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Modulating fat digestion through food structure design
Accepted Manuscript Modulating fat digestion through food structure design
Qing Guo, Aiqian Ye, Nick Bellissimo, Harjinder Singh, Dérick Rousseau PII: DOI: Reference:
S0163-7827(17)30038-3 doi:10.1016/j.plipres.2017.10.001 JPLR 951
To appear in:
Progress in Lipid Research
Received date: Revised date: Accepted date:
3 August 2017 5 October 2017 6 October 2017
Please cite this article as: Qing Guo, Aiqian Ye, Nick Bellissimo, Harjinder Singh, Dérick Rousseau , Modulating fat digestion through food structure design. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Jplr(2017), doi:10.1016/j.plipres.2017.10.001
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ACCEPTED MANUSCRIPT
Modulating fat digestion through food structure design
Qing Guo,1* Aiqian Ye,2, 3 Nick Bellissimo,4 Harjinder Singh,2,
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Department of Chemistry and Biology, Ryerson University, Toronto, ON, CANADA 2
Riddet Institute, Massey University, Palmerston North 4442, NEW ZEALAND
Massey Institute of Food Science and Technology, Massey University, Palmerston North 4442, NEW ZEALAND
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School of Nutrition, Ryerson University, Toronto, ON, CANADA
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Dérick Rousseau,1*
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*Corresponding authors:
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Qing Guo, Ryerson University, Department of Chemistry and Biology, 350 Victoria St., Toronto, ON M5B 2K3, CANADA
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Email: [email protected]
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Dérick Rousseau, Ryerson University, Department of Chemistry and Biology, 350 Victoria St., Toronto, ON M5B 2K3, CANADA Email: [email protected] Phone: +1-416-979-5000 x2155; Fax: +1-416-979-5044
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ACCEPTED MANUSCRIPT Abstract Dietary fats and oils are an important component of our diet and a significant contributor to total energy and intake of lipophilic nutrients and bioactives. We discuss their fate in a wide variety of engineered, processed and naturally-occurring foods as they pass through the gastrointestinal
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tract and the implicit role of the food matrix within which they reside. Important factors that
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control fat and oil digestion include: 1) Their physical state (liquid or solid); 2) Dispersion of oil
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as emulsion droplets and control of the interfacial structure of emulsified oils; 3) The structure and rheology of the food matrix surrounding dispersed oil droplets; and 4) Alteration of
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emulsified oil droplet size and concentration. Using examples based on model foods suc h as
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emulsion gels and everyday foods such as almonds and cheese, we demonstrate that food structure design may be used as a tool to modulate fat and oil digestion potentially resulting in a
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number of targeted physiological outcomes.
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Keywords: Food fats and oils; Food structure; Gastrointestinal tract; Digestion; Emulsion
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Abbreviations: 2-MAGs, 2-monoacylglycerols; β-lg, β- lactoglobulin; BSSL, bile salt stimulated lipase; FFAs, free fatty acids; GIT, gastrointestinal tract; HMPC, hydroxypropyl methylcellulose;
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IKO, LPCAT3 knockout; L, linoleic acid; LCT, long-chain triacylglycerol; LPCAT3, lysophosphatidylcholine acyltransferase 3; M, medium-chain fatty acids; MCT, medium-chain triacylglycerol; MFGM, milk fat globule membrane; NEFAs, non-esterified fatty acids; O/W, oil-in-water; SCT, short-chain triacylglycerol; SFC, solid fat content; TAGs, triacylglycerols
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ACCEPTED MANUSCRIPT 1. Introduction The overconsumption of foods rich in fats and oils is an important factor contributing to obesity and has been linked to an increased incidence of chronic diseases such as diabetes, heart disease and certain cancers [1-3], which has resulted in a significant healthcare burden in many countries
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[4]. The judicious reduction in intake of fats and oils is a widely-recommended, non-invasive
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prevention strategy to mitigate obesity and related chronic diseases. However, feelings of
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hunger, food cravings, and easily-accessible, palatable fatty foods have made it difficult to control their intake levels in certain populations [5]. The development of foods that reduce fat
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bioaccessibility or appetite represents a potential solution for weight management [6]. As well,
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meeting the dietary needs of other segments of the population such as the physical active or chronically ill represents a research opportunity that requires greater knowledge and
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understanding of how the human digestive system treats, transports and utilizes food lipids.
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Food fats and oils are incorporated into different processed food s as ingredients (e.g., milkfat in
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yogurt and cheese, vegetable oil in salad dressing and animal fat in sausages), during food preparation as bulk materials (frying oil or butter on toast) or exist in naturally-occurring foods
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in the form of emulsions where oil droplets are encased within a continuous liquid or solid
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matrix (e.g., dairy milk, seeds, and nuts). Fats and oils thus exist in a variety of forms in the bulk or within a food matrix. The structure (or matrix) of a food is defined as the organization of its constituent molecules at multiple spatial length scales (Figure 1) [7]. It plays a vital role in how food interacts with the gastrointestinal tract (GIT) (e.g., bodily fluids and receptors) and the resulting release and uptake of nutrients. Most foods are complex, heterogeneous materials composed of structural elements or domains (co-)existing as solids, liquids and/or gases where length scales span < 1 nano metre 3
ACCEPTED MANUSCRIPT to millimetres (Figure 1) [7]. The structure of all foods is provided by nature or imparted during processing and preparation. Food structure design is the dedicated conception and fabrication of foods in such a way as to attain specific structures, functions or properties. Beyond contributing to texture, sensory properties, shelf life and stability, control of food structure can alter the
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kinetics and extent of food digestion (e.g., lipid digestion) [8, 9]. For example, nutrient
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absorption in peanuts in different physical forms has been found, with less fat absorbed from
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nuts than the butter or oil [10]. From a food product design standpoint, lipid digestion, which largely determines the absorption of fatty acids and other lipophilic nutrients/bioactives, can be
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modulated by controlling the access of lipases onto the oil-water interface via alteration of the
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surrounding food matrix [11, 12].
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Triacylglycerols (TAGs) are the dominant lipid form in foods, these consisting of three fatty acids esterified to a glycerol backbone. The nature of the constituent fatty acids (alkyl chain
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length, degree of unsaturation) and their positional distribution (sn-1, 2 or 3) will dictate their
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physical properties, digestibility and impact on human health. TAG digestion and absorption are complex processes and involve a number of physicochemical
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events along the GIT. Following ingestion of fats or oils, the first step in TAG absorption is
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hydrolysis in the mouth and stomach where they are hydrolyzed by lingual and gastric lipases that preferentially hydrolyze the sn-3 position of TAGs to generate fatty acids in their free form [(free fatty acidsFFAs)] or non-esterified fatty acids (NEFAs) and 1,2-diacylglycerols [13-15]. In healthy adults, there occurs ~ 10-30 % lipolysis of ingested TAGs in the stomach [16, 17]. The ensuing step is further TAG breakdown in the duodenum where pancreatic lipase adsorbs onto the surface of pre-existing oil droplets, or those formed in-situ by interacting with adsorbed bile salts and other surfactants in the stomach and small intestine. Pancreatic lipase preferentially 4
ACCEPTED MANUSCRIPT hydrolyzes the sn-1 and sn-3 position in TAGs [15], leading to the formation of FFAs and 2monoacylglycerols (2-MAGs). The third step involves solubilization and uptake of lipolytic products by the enterocytes, which are then encapsulated in self-assembled structures, such as bile salt micelles and phospholipid vesicles and transited to intestinal epithelial cells for
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absorption [18]. These self-assembled structures increase the aqueous concentration of lipolytic
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products, which enhances their absorption rate. In the last step, long-chain FFAs (long-chain: >
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12C and very long-chain: ≥ 20C) and 2-MAGs are transported into the endoplasmic reticulum inside the enterocytes, where they are re-synthesized into TAGs [19-21]. These TAGs are
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packaged with cholesterol, lipoproteins and other lipids into chylomicrons that are distributed to
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different cells via the lymphatic system and then onwards to systemic circulation [22]. By contrast, short- (< 6C) and medium-chain (6C - 12C) FFAs are transported bound to serum
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albumin and leave the enterocytes through the portal vein [20].
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Internationally, the agri- food sector is in the midst of undergoing a revolution where food is no
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longer simply seen as a low- margin commodity. Rather, it is increasingly being seen as source of improved health and increased revenue potential. For example, the introduction of healthier food
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options by agri- food manufacturers is resulting in greater sales, thus benefiting margins further
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as health-conscious consumers generally pay more for foods that they believe is healthy for them. According to a global health and wellness report of 30,000 people, 90% of consumers are willing to pay more for foods with added quality and benefits [23]. In this context, judicious control of lipid digestion opens up the possibility of developing new food products with added health benefits such as controlled lipid bioaccessibility and release of specific fatty acids from food fats and oils within the GIT. As a result, deliberate control of food structure for controlled
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ACCEPTED MANUSCRIPT lipid delivery is an area of rapidly- growing research. In this review, we identify some of the latest research trends in lipid digestion and the implicit role played by food structure design.
2. Dietary TAGs
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The fatty acid distribution within naturally-occurring TAGs is not random [24, 25]. The
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taxonomic patterns of vegetable oils consist of TAGs obeying the 1, 3-random-2-random distribution, with saturated fatty acids being located almost exclusively at the 1, 3-positions of
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TAGs [26]. Conversely, fats from the animal kingdom (tallow, lard ) are quite saturated at the sn-
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2 position [27].
In describing the physical properties of food lipids, one must consider whether they are in the
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liquid or solid state. At room temperature, processed oils will be liquid whereas fats will be
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solid- like. Compositionally, oils will primarily consist of mono or poly- unsaturated fatty acids whereas fats will be generally much higher in saturated fatty acid content. Along with the degree
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of unsaturation, the extent to which neighbouring fatty acids interact both intra- and inter-
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molecularly will dictate whether a TAG exists in the liquid or solid state [28]. During crystallization, TAG molecules adopt a “tuning- fork” or “chair” conformation with, for example,
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the sn-2 fatty acid pointing in the opposite direction to the sn-1 and sn-3 fatty acids, which results in the formation of distinct TAG crystalline lamellae that assemble into a fat crystal network [29]. Once crystallized, TAGs have different packing modes known as the α, β′ and β polymorphic forms, each with a distinct melting point [30]. For example, the melting point of tristearin (a triester of stearic acid) in the α, β′ or β form is 54, 64 and 73 °C, respectively [31]. Common fats used in processed foods include butter (milk fat), beef fat, chicken fat, pork fat (lard, bacon), stick margarine, and shortening. 6
ACCEPTED MANUSCRIPT Interesterification, hydrogenation, and fractionation are three processes available to food manufacturers to tailor the physical, and chemical properties of food lipids. Each operation is based on different principles to attain its goal. Fractionation is a physical separation process based on the distinct crystallization temperature of different TAGs; thus, crystallization at a set
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temperature is used to separate TAGs that have solidified from those tha t remain liquid.
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Hydrogenation is a chemical process leading to the saturation of double bonds present in fatty
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acids in the presence of hydrogen gas and a metal catalyst to harden fats for use as margarine and shortening base stocks, but also potentially results in the formation of trans unsaturated fatty
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acids [32]. The usage of hydrogenated fats is declining due to the negative health effects (e.g.,
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heart disease) of hydrogenated fats enriched in trans fatty acids and governmental pressures to reduce trans fat levels in food products [33, 34]. Finally, interesterification causes a fatty acid
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redistribution within and among TAGs, which can lead to substantial changes in lipid
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functionality, such as melting point or profile [32]. Fractionation and/or interesterification are common unit operations for the production of a low or “zero-trans” fats with desirable physical
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properties (e.g., a higher melting point).
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2.1. Emulsified oils and fats
In processed foods, the vast majority of fats and oils are present as emulsions. Contrary to bulk
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fats, emulsions consist of two immiscible liquids with one phase dispersed within the other as droplets. In foods, most emulsions consist of oil droplets dispersed in a continuous aqueous phase, such as a vinaigrette where vegetable oil is dispersed as droplets in a vinegar solution. To create such oil- in-water (O/W) emulsions, it is necessary to supply energy in order to subdivide the oil into micron-sized dispersed droplets within the continuous vinegar phase, which is usually achieved by high- intensity agitation. Emulsifiers such as proteins and small- molecule surfactants
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ACCEPTED MANUSCRIPT such as lecithin are used to emulsify and coat the dispersed oil droplets, which slows their separation [35]. Over time, all emulsions will separate into oil and aqueous layers, via mechanisms such as creaming, flocculation and coalescence [36]. Creaming is a separation process based on density
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differences between food oils and water, which results in the formation of an oil layer atop an
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aqueous layer, as is observed in freshly-produced milk [35]. With flocculation, two or more oil
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droplets will aggregate with one another while remaining intact [37, 38]. This step is a precursor to coalescence where flocculated droplets merge to form a single larger droplet. In practice,
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careful emulsifier composition and concentration will ensure that food emulsions remain stable
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against coalescence during their expected shelf life [39], which can range from minutes in the case of home- made vinaigrette to years in the case of mayonnaise. Emulsion breakdown in the
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human gut also depends on the choice of stabilizing surfactant or protein as these can greatly
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affect the extent and rate of oil droplet coalescence. As further described below, coalescence reduces oil droplet surface area, which slows the rate of fat digestion by the body, potentially
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impacting fat absorption and release of GIT hormones, such as those associated with satiety. As
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emulsions represent the dominant form in which fats and oils are found in natural and processed foods, this review focuses on the fate of emulsified fats and oils dispersed in different food
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matrices. We demonstrate that the properties of emulsions and the surrounding food matrix both play important roles in modulating the digestion of food fats and oils.
3. Disintegration of foods in the GIT The GIT is the anatomical ‘tube’ that extends from the mouth to the anus, including organs responsible for transit, digestion and absorption of foods. Food assimilation occurs in the upper 8
ACCEPTED MANUSCRIPT GIT, namely the mouth, esophagus, stomach and small intestine. The mouth, defined as the hollow space between the lips and the velum [40], namely contains teeth, the tongue and salivary glands. The stomach is a J-shaped enlargement of the GIT that connects the esophagus and duodenum. It is made up of four parts: the cardia, fundus, body and pylorus [41]. Antral
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contraction waves (3 cycles min-1 ) proceed from the body of the stomach towards pylorus,
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resulting in food mixing, antral grinding and gastric emptying [42]. Gastric juice containing
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pepsin and hydrochloric acid is secreted by gastric glands, with the fasting gastric pH being 1.52.0 [43, 44]. The small intestine is made up of the duodenum, jejunum, and ileum, and is where
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digestion is completed. Bile and pancreatic juices are secreted into the duodenum [41]. The pH
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of gastric chyme (which consists of partially-digested food and digestive juices) reaches 6-7 in the duodenum after mixing with intestinal juices [44]. Throughout the length of the small
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intestine, the mucosa is lined with enterocytes covered by villi and microvilli that enhance
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nutrient absorption, which mainly occurs in the duodenum and jejunum [41].
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During digestion, foods continuously interact with the GIT. The initial shape and structure of a food is modified by dilution, digestive enzymes, mechanical shearing/grinding, and changes in
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pH and ionic conditions. As a highly-dynamic process, an understanding of food breakdown in
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the human body is clearly important for food product development and nutritional assessment. As in vivo human trials, though powerful in outcome, are sometimes limited by ethical constraints [45], in vitro models that simulate the GIT are seeing increased usage to easily probe digestive phenomena. Although it remains impossible to perfectly simulate physiological conditions, in vitro digestion can provide useful information associated with in vivo processes such as fatty acid release from dispersed fats and oils [45].
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ACCEPTED MANUSCRIPT Food disintegration includes three stages: oral processing, gastric digestion and intestinal digestion. In the mouth, humans are predisposed to different patterns of food oral processing (e.g., number of chewing cycles and duration of mastication) based on the properties of the foods [40, 46]. Mastication breaks down a solid food into small particles and mixes it with saliva to
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form a cohesive bolus ready for swallowing whereas liquid foods stay in the mouth for seconds
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and are swallowed directly [40]. In general, the degree of fragmentation of solid foods increases
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with increasing food hardness [47]. Though mastication, mixing with saliva, and the friction between oral surfaces will break foods down into milli-scale particles, their microstructure will
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liquid emulsions such as salad dressings [48-51].
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remain largely intact, whether we speak of solid foods such as nuts, spaghetti, or protein gels or
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In the stomach, proteins are significantly hydrolyzed by pepsin whereas lipids are only partially digested and carbohydrates see little breakdown [41]. Larger post-oral processing food particles
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are further broken down into smaller particles (< 1-2 mm) by antral grinding [52], which along
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with gastric juices, results in significant disruption of food microstructure. Destabilization of O/W emulsions occurs during gastric digestion, the degree of which depends on the nature of
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interfacial film covering the dispersed oil droplets and the food matrix surrounding the oil
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droplets [53, 54]. During gastric processing, larger oil droplets (e.g., > 6 μm) may coalesce, cream and phase-separate in the stomach, which affects their rate of gastric emptying and ensuing digestion in the small intestine [55, 56]. However, as oil droplets are often dispersed within complex structures such as cheese and sausages, most of them may not be released at all during gastric digestion. In the small intestine, most food macronutrients are physically and chemically broken down with the aid of a series of enzymes, such as trypsin, chymotrypsin, pancreatic lipase, colipase, and α10
ACCEPTED MANUSCRIPT amylase, which facilitates their absorption [41]. Both pre-existing emulsified oils and fats or emulsions formed in-situ in the duodenum or the stomach must be exposed to the intestinal environment for hydrolysis and uptake [16, 53, 55, 57]. Together, the interfacial film and the food matrix surrounding the dispersed oil droplets as well as the composition of the oil and fat
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will modulate their intestinal digestion (Figure 2).
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The following sections highlight the influence of interactions between the GIT and model or real
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foods on lipid digestion, with a focus on the relationship between food structure and lipid digestion. We define model systems as foods with a controlled degree of complexity vs.
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naturally-occurring or processed foods which are inherently more complex given their greater
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4. Role of TAG composition on digestion
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number of co-existing, interacting ingredients and phases (liquid, solid and gas).
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TAG composition greatly affects many properties of oils and fats, such as melting point, solid fat content (SFC), crystal structure and the FFA types released during digestion. As a result, TAG
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composition is an important factor that should be considered in designing foods containing oils
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and fats. 4.1. TAG composition
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Fatty acid chain length and degree of unsaturation along with their positional distribution may impact TAG rate and extent of lipolysis. Furthermore, if TAG molecule s contain a polar group (e.g., phosphate group), there will be a significant effect on lipolysis. The rate and extent of TAG digestion during in vitro digestion will decrease with increasing fatty acid chain length in this order: short-chain triacylglycerol (SCT) > medium- chain triacylglycerol (MCT) > long-chain triacylglycerol (LCT) [58-61]. This is ascribed to the fact that FFAs released from LCTs can
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ACCEPTED MANUSCRIPT accumulate at oil droplet surfaces, thereby restricting easy lipase access to other TAGs [62, 63]. By contrast, medium or short-chain FFAs have a higher affinity for water and rapidly move into the surrounding aqueous phase after formation, making it easier for the lipase to hydrolyze as- yet unaffected TAGs [64]. However, this effect of long-chain FFAs delaying lipid digestion is
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dependent on bile concentrations as higher bile salt concentrations result in a higher rate and
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extent of LCT digestion [62, 65-67]. By contrast, the digestion of MCT is not dependent on bile
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salt concentrations [64].
The positional distribution of fatty acids on TAG molecules can be modified using
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interesterification, thereby influencing lipid digestion. For example, in a mixed system with
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structured oils containing both medium-chain fatty acids (M) and linoleic acid (L), Nagata et al. found that in vitro TAG hydrolysis by pancreatic lipases was 2–3- fold higher for MLM vs. LML
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TAGs, with the corresponding serum TAG levels higher in rats fed MLM type vs. LML. This
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confirmed that the positional distribution of fatty acids within TAGs (especially long-chain fatty acids at the sn-1 or sn-3 positions) affected lipid digestion [59]. Interestingly, soybean oil (an
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LCT) and coconut oil (an MCT) showed similar bioavailability (97 – 99 %) in an animal study,
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suggesting the need for further studies in this area [68]. The degree of unsaturation of TAGs (i.e., poly vs. mono- unsaturation) does not appear to
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significantly affect lipid digestion, though work remains to be done in this area. Of the scarce reports available, Zhang et al. and Ozturk et al. reported that the fish oil emulsions containing very long-chain polyunsaturated fatty acids (e.g., eicosapentaenoic acid and docosahexaenoic acid) showed FFA release profiles similar to corn oil emulsions, which are rich in oleic acid, which is monounsaturated, and linoleic acid, which contains two double bonds [61, 69].
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ACCEPTED MANUSCRIPT Dietary phospholipids, a major component of membrane lipids, have an amphipathic structure with hydrophobic properties conferred by the fatty acid chains at the sn-1 and sn-2 positions and hydrophilic properties conferred by the sn-3 phosphate group. Dietary phospholipids can affect lipid digestion and absorption through different mechanisms [22, 70]. For example, pancreatic
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phospholipase A2-knockout mice were shown to be resistant to high- fat diet- induced obesity
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[71], perhaps due to the limited release of MAGs and lysophosphatidylcholine (as surfactants)
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given that the lack of phospholipase can lessen the ability of bile salts to form mixed micelles
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that remove lipolytic products from the oil-water interface during digestion [22]. Phospholipids are critical for dietary lipid absorption [72]. The remodeling enzyme
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lysophosphatidylcholine acyltransferase 3 (LPCAT3) is an enzyme that modulates membrane
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phospholipid composition [73]. A recent study showed reduced plasma TAG levels were observed in intestine-specific LPCAT3 knockout (IKO) mice [72]. By contrast, administration of
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16:0/20:4 phosphatidylcholine to IKO intestines increased fatty acid uptake to a level
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comparable to control intestines, implying phospholipids played an important role in lipid passive absorption through the membrane of enterocytes.
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4.2. Physical state – oil vs. fat
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The physical state of fats and oils can significantly impact their digestibility. It was recently shown in an in vitro study that emulsified fats with a higher SFC were less susceptible to lipolysis than their lower-SFC counterparts [74], likely as result of pancreatic lipase access to TAGs being more limited at higher SFC. In vivo animal and human studies have also both shown that TAGs in the solid state have a much lower bioavailability than liquid TAGs [55, 68, 75]. Interestingly, O/W emulsions prepared using rapeseed oil (which is liquid) resulted in much lower hunger ratings than emulsions containing hydrogenated palm fat (which is a hard fat) in a 13
ACCEPTED MANUSCRIPT double-blind, randomized and crossover-designed human trial, probably due to the slow digestion and lower bioaccessibility of the palm fat rather than differences associated with the constituent fatty acids [55].
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5. Interfacial structure of food emulsions and lipid digestion
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An O/W emulsion consists of emulsified lipids dispersed as droplets within a continuous aqueous phase. The interfacial film at the droplet surface is key in determining emulsion stability
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and digestibility. Key factors dictating the properties of interfacial films include surface charge, film thickness, and surface activity, which can all greatly impact susceptibility to enzymatic
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attack.
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5.1. Emulsifier types
Proteins, polysaccharides and small- molecule surfactants are widely used in food applications.
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Proteins can form an interfacial film on the surface of droplets whose properties are influenced
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by the surface charge and hydrophobicity of constituent amino acids and their 3D rearrangement following interfacial adsorption [76]. Some polysaccharides possess surface activity that
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originates from either the non-polar chemical groups attached to the hydrophilic polysaccharide
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backbone (e.g., modified cellulose) or the presence of a protein moiety covalently or physically linked to the polysaccharide (e.g., pectin) [77]. Small- molecule surfactants are much smaller but much more surface-active than proteins and polysaccharides, and decrease surface tension to a larger extent, which typically results in emulsions with a lengthier kinetic stability under quiescent conditions [76]. The digestion of protein-stabilized emulsions as affected by protein structural and biochemical factors has been summarized in a previous review [53]. Nominally, a protein film present at an 14
ACCEPTED MANUSCRIPT oil- water interface will be easily broken down by proteases and displaced by bile salts [78]. Protein properties generally have little effect on lipid digestion, though this is highly dependent on protein type [53]. Compared with animal proteins, interfacial films formed by plant proteins may provide enhanced protection against lipolysis during digestion. For example, as the
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insolubility and hydrophobicity of deamidated wheat gliadins are much higher than dairy
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proteins [79], they form a more compact interfacial film that is resistant to displacement by bile
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salts. This hinders the diffusion of lipase towards oil droplet surfaces, resulting in a lower extent of lipid digestion [80]. Similarly, soybean proteins are more resistant than β- lactoglobulin (β- lg –
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a dairy whey protein) to interfacial displacement by bile salts at the oil-water interface [81],
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leading to the delayed lipid digestion [82], the cause being their two different fractions that differ greatly in structure from β- lg: a hydrophilic polysaccharide that is esterified to a polypeptide [83].
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The former protects the emulsion droplet surface by forming a thick hydrated layer whereas the
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latter is anchored into the oil droplet core.
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Most polysaccharides are used to thicken foods as they have little propensity towards emulsification, given their lack of surface activity [77]. Other polysaccharides, such as gum
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Arabic, modified starches, modified celluloses, pectin, and galactomannans, show some
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surface/interfacial activity [84]. Although the emulsification capacity of polysaccharides is not efficient compared to proteins and small- molecule surfactants, they can form a thicker interfacial film around dispersed oil droplets. For examples, hydroxypropyl methylcellulose (HMPC) is a chemically modified cellulose with a high molecular weight (100 000 g·mol-1 ) used in foods as a thickener, bulking agent, fibre source and emulsifier. At oil droplet surfaces, its adsorbed layer is several hundreds of nanometres thick, which is much greater than that of protein layers (1-10 nm) [85, 86]. When present in emulsions, low concentrations of bile salts will disrupt, though not
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ACCEPTED MANUSCRIPT completely displace, HMPC adsorbed to an oil- water interface [82, 87-89]. In this case, retarded lipolysis is mainly attributed to the binding between bile salts a nd any unadsorbed HMPC present in the emulsion’s aqueous phase [89]. Finally, food- grade surfactants (e.g., lecithin, phospholipids and polysorbates), though widely
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used in processed foods, play a limited role in modulating in vitro lipid digestion as they are
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easily displaced by bile during digestion [70, 90-95]. 5.2. Adsorbed multilayers
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Multilayers are produced by attaching alternating layers of oppositely-charged biopolymers onto emulsion droplets using layer-by- layer deposition. To do so, an O/W emulsion is initially
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stabilized by a charged water-soluble emulsifier such as most proteins or lecithin. Afterwards, an
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oppositely-charged biopolymer such as chitosan, gum Arabic, carrageenan, pectin and chitosan is deposited under different pH and ionic strength conditions. This process is repeated until the
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desired number of multilayers is attained. Such multilayers are thought to confer more protection
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against lipolysis than a monolayer. However, pH plays a huge role in this eventuality. After food ingestion, the pH in the stomach decreases from 5 – 6 to 1.5 – 2.0 [96, 97], whereas the pH of
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chyme increases to ~ 6 - 7 after entering the duodenum and mixing with intestinal juices [41]. As
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the interaction between anionic and cationic biopolymers is pH-dependent [98], the large variations of pH in the GIT will greatly affect multilayer stability [99], which will subsequently impact dispersed oil digestibility [100-102]. 5.3. Solid particles and solid interfacial shells Compared with molecular emulsifiers, micro or nano-scale particles can anchor to the oil-water interface with a very high desorption energy that renders them virtually irreversibly attached [103]. As a result, they limit the ability of bile salts and enzymes to physically contact the 16
ACCEPTED MANUSCRIPT surface of dispersed oil droplets, leading to a decreased extent of digestion. For example, Sarkar et al. formed whey protein microparticles through homogenization of a heat- induced 10% whey protein isolate gel [104], showing that these emulsions were stable during in vitro gastric digestion resulting in delayed lipid digestion during subsequent intestinal digestion compared
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with a control whey protein-stabilized emulsion. In general, if digestible, particles whether
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carbohydrate, fat or protein-based, will show a limited ability to retard the digestion of
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emulsified lipids [105, 106]. By contrast, non-digestible particles can greatly suppress lipid digestion. As an example, nanocrystals based on chitin, an abundant natural amino-
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polysaccharide [107], can significantly retard the rate and extent of lipid digestion compared to
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protein-stabilized emulsions, given their insolubility, lack of digestibility, and strong adsorption
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to the oil-water interface [108].
An alternative approach that may delay lipid digestion consists of using thermosensitive species
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such as starch granules, which can form continuous solid shells around dispersed oil droplets.
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For example, Sjöö et al. exposed O/W emulsions stabilized by starch shells to simulated GIT conditions and showed that the extent of lipid digestion was lowest when the starch had
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gelatinized enough to create a dense layer around the oil droplets but hadn’t swollen into a
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porous structure that granted access to the lipase [105, 109].
6. Food gel matrix and lipid digestion When oil droplets are dispersed in a solid-like food matrix (e.g., cheese or yogurt), the structure of the surrounding food matrix becomes the dominant factor controlling digestion [110]. During digestion, the 3D network structure within a food matrix (i.e., the spatial architecture resulting from the assembly of macromolecules such as proteins, polysaccharides and lipids into a 17
ACCEPTED MANUSCRIPT coordinated network) can obstruct the diffusion of enzymes towards the surface of dispersed oil droplets. Compared to interfacial films, the solid like-food matrix is potentially capable of providing enhanced protection against lipolysis. A broad range of processed food products, including yogurt, cheese, some sauces, and
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reformulated meat products consist in part of such p rotein-based emulsion gels [110]. As a
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model system, a number of studies have investigated the role of the structure of whey protein
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emulsion gels on lipid digestion [48, 54, 74, 97, 111-113]. In these studies, gels with different microstructures were formed by heating whey protein emulsions containing sub-micron oil
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droplets in the presence of different salt concentrations, which was a necessary conditions for
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gelation [48, 112]. Softer gels containing lower NaCl concentrations (< 50 mM) consisted of a homogeneous protein matrix while harder gel produced at higher NaCl concentrations (> 100
M
mM) consisted of a porous protein network (Figure 3A). This difference in gel microstructure
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was an important contributor to differences in dispersed oil digestion. During in vivo mastication, few oil droplets were released from both hard and soft gels (Figure 3B) [48, 112]. During gastric
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digestion, however, the soft gel rapidly dissolved whereas the hard gel only broke down in
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smaller particles, and showed limited oil droplet release (Figure 3C) [48, 54, 97]. Finally, during intestinal digestion, the soft gel presented a digestion behaviour similar to a liquid whey protein
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emulsion whereas remnants of the hard gel remained, thereby leading to a lower lipolysis rate (Figure 3D) [113].
In another example, emulsion-filled hydrogel beads consisting of alginate or κ-carrageenan were resistant to disintegration during oral, gastric and intestinal digestion [114-116]. Here, the digestion of oil droplets within the beads was greatly delayed compared to free oil droplets. This largely resulted from the hydrogel matrix restricting the diffusion of lipase to the surfaces of oil
18
ACCEPTED MANUSCRIPT droplets, the presence of electrostatic interactions between the biopolymers and pancreatic lipase at neutral pH and the non-digestibility of the biopolymer mixture. By contrast, a rice starchbased gel was shown ineffective at protecting incorporated oil droplets against hydrolysis [117],
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due to its low gel strength, swelling and high digestibility [105, 118-120].
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7. Effect of oil droplet size on lipid digestion
In vitro digestion studies have shown that the original droplet size of an emulsion and the change
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in droplet size during digestion greatly influence the rate of lipid digestion, namely that a larger droplet size will almost invariably result in a lower rate of digestion [121-125]. In general, oil
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droplet size increases upon gastric and intestinal digestion due to flocculation and coalescence,
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though this highly depends on the original size and surface properties of the oil droplets [126,
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127].
Recently, the gastric emptying, creaming and phase separation of acid-stable and acid-unstable
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O/W emulsions were investigated using magnetic resonance imaging [128]. This study showed
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that acid-stable emulsions largely retained their gastric stability throughout the 180- min scanning period and their duodenal contents were homogeneous. By contrast, acid-unstable emulsions
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underwent structural changes with evidence of fat phase creaming and droplet flocculation, and as a result were emptied more quickly from the stomach than the acid-stable emulsions. In another study, Armand et al found that both fine (0.7 μm) and coarse (10 μm) acid-stable emulsion droplets stabilized by lecithin and dairy proteins were relatively stable in the human stomach based on the small change in oil droplet size observed with time [17]. As well, Steingoetter et al. reported that a reduction in droplet size by 2 orders of magnitude (0.3 vs. 52 µm) delayed gastric emptying by 38 min for acid-stable emulsions in a human trial [55]. These in 19
ACCEPTED MANUSCRIPT vivo human studies demonstrate that the gastric stability and particle size of food emulsions greatly affects the transit of emulsified oils and fats in the GIT and may further influence lipid digestion, which needs to be considered when formulating foods.
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8. Lipid digestion in natural and processed foods
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In ‘real’ food products, lipids are dispersed within a liquid or solid food matrix which is normally more complex and heterogeneous than the model systems discussed above. In the
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context of this review, it is therefore pertinent to pose a question: Can novel approaches to modulating lipid digestion in real food products be achieved on the basis of knowledge of
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digestion in model foods? Some evidence in support of this view is briefly presented below for a
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number of cases: almonds and almond milk, bovine and human milk, infant formula and firm cheese.
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8.1. Almonds
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Almonds are a valuable dietary source of lipids, proteins, dietary fibre, vitamins, minerals, phenolic compounds and phytosterols. Their structure is representative of many nuts and seeds
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(e.g., walnut, peanut and sesame seed). Oil bodies, which are the oil-bearing structures that may
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represent over 50 % of the nut weight, are located within thin-walled cells (Figure 4) [129]. Intra-cellular lipid bodies are ∼1-3 μm in diameter and stabilized by a monolayer of phospholipids and oil body-specific proteins mostly from the oleosin family [130]. The release of oil bodies from almond cells or the diffusion of lipase towards these cells is necessary for lipolysis. Approximately 10% of lipids in raw and roasted almonds have been observed to be released from almonds upon mastication with the cells remaining largely intact [49]. The particle size of 20
ACCEPTED MANUSCRIPT whole almonds in another study decreased to 500 and 350 μm for raw and roasted almonds, respectively, after mastication and in vitro gastric digestion [131]. The rate and extent of lipid digestion of almond cells were much lower than that of the isolated o il bodies (22 vs. 69% hydrolysis after 1 h digestion) during in vitro intestinal digestion [132]. In vitro digestion studies
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are highly consistent with in vivo human trials. Berry et al. found that the postprandial increase in
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plasma TAG levels was lowered by 74% after whole almond meal consumption vs. almond flour
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[11]. In another study, a large proportion of cells remained intact and undigested oil bodies were found in faeces after consumption of an almond diet [133]. From in vitro oral to duodenal
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digestion, no significant changes were observed in the cell wall composition of almonds [131].
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Intact almond cells retained their intracellular lipids even after long periods of digestion (20 hours), and encapsulated lipids contained in intact almond cells could only be digested by lipases
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that slowly diffused through to the cell wall [132]. However, lipases easily penetrated the cell
ED
wall of damaged cells to access intracellular lipids [132]. Therefore, the digestion and bioaccessibility of lipids in almonds was regulated by the structure and properties of the cell
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walls surrounding the oil bodies.
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Due to the low bioaccessibility of TAGs in whole almonds, oil bodies are often studied after their
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extraction and resuspension in an aqueous environment to form a milk [134]. When oil bodies are released from the cells, the protease and lipase can easily access their surface to then hydrolyze the incorporated TAGs. Digestion of such oil bodies has been recently studied both in vitro and in vivo, where it was shown that an almond oil body emulsion behaved similarly to a protein-stabilized O/W emulsion in a simulated GIT environment [135]. An in vivo animal study showed that almond milk tended to coalesce under gastric conditions, which differed from in vitro digestion [135, 136], suggesting that gastric lipase, which was absent in the in vitro study, played an important role in lipid
21
ACCEPTED MANUSCRIPT digestion. Overall, these results demonstrate that both the interfacial structure of emulsion droplets and that of the surrouding matrix play a preeminent role in dispersed oil digestion. 8.2. Milk and infant formula Milk is a complex food emulsion consisting of ~ 3 - 4 μm fat globules, various proteins and
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carbohydrates dispersed in an aqueous serum [137, 138]. Native milk fat globules are stabilized
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by a lipid trilayer rich in integral and peripheral proteins in the milk fat globule membrane
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(MFGM) [138, 139]. Thermal treatments such as pasteurization are commonly used to destroy
US
potential pathogens, allowing for safe consumption and a long shelf life. Such thermal treatments also result in denaturation of some MFGM proteins, aggregation of milk serum proteins and
AN
interactions between the MFGM and these proteins, thereby influencing milk digestion [140,
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141]. De Oliveira et al. compared the kinetics of in vitro lipolysis of raw versus pasteurized human milk from a donor milk bank at the University Hospital Centre in Rennes, France [141].
ED
After 60 min of gastric digestion, more severe flocculation and aggregation occurred in raw milk.
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By contrast, there was no large variation in the particle size distribution of pasteurized milk during gastric digestion, which appeared related to the protective effect of pasteurization- induced
CE
protein aggregates adsorbed at the surface of fat globules. The gastric lipolysis rate of
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pasteurized milk was also significantly lower than that of raw milk, which was ascribed to inactivation of bile salt-stimulated lipase (BSSL) (an endogenous lipase of human milk) by pasteurization and, as above, protection by adsorbed protein aggregates. By contrast, a n animal study showed that pasteurization did not greatly affect gastric lipolysis of bovine milk (origin: pasture-raised Friesian cows on a dairy farm in Palmerston North, New Zealand) where BSSL is absent [142]. This suggests that BSSL plays an important role in the lipid digestion of human milk during gastric digestion. In a randomized controlled human trial, pre-term infants were fed
22
ACCEPTED MANUSCRIPT raw or pasteurized milk collected from their own mothers to evaluate the effect of pasteurization on milk digestion [143]. In the stomach, the specific surface area of milkfat globules in pasteurized milk was larger than that of raw milk, however their rates of lipolysis showed no difference, strongly suggesting enhanced protection by heat- induced structural changes in human
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milk protein. Other studies have shown that changes in MFGM surface composition induced via
IP
homogenization do not significantly affect lipolysis compared with raw milk [144, 145]. Finally,
CR
in a comparative study on infant formula and human milk, the extent of lipid digestion between the two was no different [146, 147], even though vegetable oil droplets in infant formula were 10
US
x smaller than milkfat globules in mother’s milk (~ 0.4 vs ~ 4 μm). This suggested that the
AN
MFGM was more susceptible to digestion than typical interfacial protein layers surrounding vegetable oil droplets [146]. Such studies demonstrate the need for further research that fully
M
addresses the role of interfacial structure on lipolysis in infant formula and associated products.
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8.3. Cheese
Processed dairy products like cheese and yogurt are food emulsions with oil droplets
PT
incorporated within a solid or semi-solid matrix. Processing steps such as heating applied to
CE
make these products greatly influence the structural characteristics and the properties of the protein matrix, which will largely determine product disintegration, diffusion of digestive
AC
enzymes into the matrix, and nutrient release. Studies have shown that peptides and FFAs are more easily released from milks and yogurts (which are liquid and semi-solid matrices, respectively) vs. cheeses (which are solid matrices) owing to easier breakdown of the food matrix and greater accessibility by digestive enzymes in the former two [148, 149]. Yogurts have shown similar proteolysis and FFA release kinetics to fluid milk likely due to the formation of soft clots by milk protein during gastric digestion [150-
23
ACCEPTED MANUSCRIPT 152]. For cheese, the structural characteristics and hardness are determinants of lipid digestion. Fang et al. compared the disintegration and lipolysis of cheeses with different textural properties [153], and found that regular Cheddar cheese had a significantly higher extent of lipid digestion than light Mozzarella cheese. The larger fat globules in Cheddar cheese acted as weak points in
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its microstructure and texture, which led to a greater decrease in hardness and greater
IP
disintegration during in vitro digestion. By contrast, light Mozzarella consisted of a denser
CR
fibrous protein matrix due to the stretching step that occurs during its fabrication. Its protein matrix showed a lower rate of disintegration and protein hydrolysis, thereby provid ing enhanced
US
protection to dispersed fat and hence a lower extent of digestion [153]. The presence of calcium
AN
in cheese plays a significant role on texture and structure. Ayala-Bribiesca et al. found that addition of calcium to Cheddar cheese during production greatly increased its firmness, and
M
decreased its disintegration rate during digestion, but enhanced lipid digestion [154]. They
ED
ascribed this behaviour to the formation of calcium soaps of long-chain fatty acids that helped remove FFAs from the oil- water interface as well as the higher degree of fat aggregation it
PT
induced [62].
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These various examples show that the properties of emulsified lipids and the surrounding matrix
AC
can significantly change the rate and extent of lipid digestion, strongly supporting the concept of food structure design as a tool to modulate lipid digestion in foods.
9. Concluding remarks and future directions Food structure design may be used as a tool to develop foods that permit control over the location, extent and rate of release of food fats and oils within the GIT. As most studies on this topic have been carried out using a simulated GIT environment, further validation of novel 24
ACCEPTED MANUSCRIPT approaches to controlling lipid digestion in processed foods requires in vivo human trials to fully understand the digestion and fate of emulsified lipids in real food products. Doing so will help decipher the relationship between dietary fat composition and structure on physiologic mechanisms regulating lipid digestion and absorption as well as outcomes such as enhanced
T
satiety via the ileal brake in test populations [6, 12, 155-157]. Moving forward, food structure
IP
design should continue to play an increasingly important role in the development of foods where
AC
CE
PT
ED
M
AN
US
CR
targeted health benefits are desired.
25
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ACCEPTED MANUSCRIPT Figure captions
Figure 1 Some structural elements in foods and relevant length scales. Redrawn with permission
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Figure 2 Simplified schematic of emulsified lipids in a food matrix.
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Figure 3 Structural changes in a firm whey protein emulsion gel containing small oil droplets
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proteins. A, B, C and D represent the original gel, gel bolus, gastric digesta at 60 min, and
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Figure 4 Transmission electron micrograph image of almond kernel showing oil bodies (grey
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Qing Guo, Aiqian Ye, Nick Bellissimo, Harjinder Singh, Dérick Rousseau PII: DOI: Reference:
S0163-7827(17)30038-3 doi:10.1016/j.plipres.2017.10.001 JPLR 951
To appear in:
Progress in Lipid Research
Received date: Revised date: Accepted date:
3 August 2017 5 October 2017 6 October 2017
Please cite this article as: Qing Guo, Aiqian Ye, Nick Bellissimo, Harjinder Singh, Dérick Rousseau , Modulating fat digestion through food structure design. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Jplr(2017), doi:10.1016/j.plipres.2017.10.001
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ACCEPTED MANUSCRIPT
Modulating fat digestion through food structure design
Qing Guo,1* Aiqian Ye,2, 3 Nick Bellissimo,4 Harjinder Singh,2,
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Department of Chemistry and Biology, Ryerson University, Toronto, ON, CANADA 2
Riddet Institute, Massey University, Palmerston North 4442, NEW ZEALAND
Massey Institute of Food Science and Technology, Massey University, Palmerston North 4442, NEW ZEALAND
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School of Nutrition, Ryerson University, Toronto, ON, CANADA
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4
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Dérick Rousseau,1*
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*Corresponding authors:
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Qing Guo, Ryerson University, Department of Chemistry and Biology, 350 Victoria St., Toronto, ON M5B 2K3, CANADA
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Email: [email protected]
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Dérick Rousseau, Ryerson University, Department of Chemistry and Biology, 350 Victoria St., Toronto, ON M5B 2K3, CANADA Email: [email protected] Phone: +1-416-979-5000 x2155; Fax: +1-416-979-5044
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ACCEPTED MANUSCRIPT Abstract Dietary fats and oils are an important component of our diet and a significant contributor to total energy and intake of lipophilic nutrients and bioactives. We discuss their fate in a wide variety of engineered, processed and naturally-occurring foods as they pass through the gastrointestinal
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tract and the implicit role of the food matrix within which they reside. Important factors that
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control fat and oil digestion include: 1) Their physical state (liquid or solid); 2) Dispersion of oil
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as emulsion droplets and control of the interfacial structure of emulsified oils; 3) The structure and rheology of the food matrix surrounding dispersed oil droplets; and 4) Alteration of
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emulsified oil droplet size and concentration. Using examples based on model foods suc h as
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emulsion gels and everyday foods such as almonds and cheese, we demonstrate that food structure design may be used as a tool to modulate fat and oil digestion potentially resulting in a
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number of targeted physiological outcomes.
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Keywords: Food fats and oils; Food structure; Gastrointestinal tract; Digestion; Emulsion
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Abbreviations: 2-MAGs, 2-monoacylglycerols; β-lg, β- lactoglobulin; BSSL, bile salt stimulated lipase; FFAs, free fatty acids; GIT, gastrointestinal tract; HMPC, hydroxypropyl methylcellulose;
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IKO, LPCAT3 knockout; L, linoleic acid; LCT, long-chain triacylglycerol; LPCAT3, lysophosphatidylcholine acyltransferase 3; M, medium-chain fatty acids; MCT, medium-chain triacylglycerol; MFGM, milk fat globule membrane; NEFAs, non-esterified fatty acids; O/W, oil-in-water; SCT, short-chain triacylglycerol; SFC, solid fat content; TAGs, triacylglycerols
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ACCEPTED MANUSCRIPT 1. Introduction The overconsumption of foods rich in fats and oils is an important factor contributing to obesity and has been linked to an increased incidence of chronic diseases such as diabetes, heart disease and certain cancers [1-3], which has resulted in a significant healthcare burden in many countries
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[4]. The judicious reduction in intake of fats and oils is a widely-recommended, non-invasive
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prevention strategy to mitigate obesity and related chronic diseases. However, feelings of
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hunger, food cravings, and easily-accessible, palatable fatty foods have made it difficult to control their intake levels in certain populations [5]. The development of foods that reduce fat
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bioaccessibility or appetite represents a potential solution for weight management [6]. As well,
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meeting the dietary needs of other segments of the population such as the physical active or chronically ill represents a research opportunity that requires greater knowledge and
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understanding of how the human digestive system treats, transports and utilizes food lipids.
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Food fats and oils are incorporated into different processed food s as ingredients (e.g., milkfat in
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yogurt and cheese, vegetable oil in salad dressing and animal fat in sausages), during food preparation as bulk materials (frying oil or butter on toast) or exist in naturally-occurring foods
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in the form of emulsions where oil droplets are encased within a continuous liquid or solid
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matrix (e.g., dairy milk, seeds, and nuts). Fats and oils thus exist in a variety of forms in the bulk or within a food matrix. The structure (or matrix) of a food is defined as the organization of its constituent molecules at multiple spatial length scales (Figure 1) [7]. It plays a vital role in how food interacts with the gastrointestinal tract (GIT) (e.g., bodily fluids and receptors) and the resulting release and uptake of nutrients. Most foods are complex, heterogeneous materials composed of structural elements or domains (co-)existing as solids, liquids and/or gases where length scales span < 1 nano metre 3
ACCEPTED MANUSCRIPT to millimetres (Figure 1) [7]. The structure of all foods is provided by nature or imparted during processing and preparation. Food structure design is the dedicated conception and fabrication of foods in such a way as to attain specific structures, functions or properties. Beyond contributing to texture, sensory properties, shelf life and stability, control of food structure can alter the
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kinetics and extent of food digestion (e.g., lipid digestion) [8, 9]. For example, nutrient
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absorption in peanuts in different physical forms has been found, with less fat absorbed from
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nuts than the butter or oil [10]. From a food product design standpoint, lipid digestion, which largely determines the absorption of fatty acids and other lipophilic nutrients/bioactives, can be
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modulated by controlling the access of lipases onto the oil-water interface via alteration of the
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surrounding food matrix [11, 12].
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Triacylglycerols (TAGs) are the dominant lipid form in foods, these consisting of three fatty acids esterified to a glycerol backbone. The nature of the constituent fatty acids (alkyl chain
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length, degree of unsaturation) and their positional distribution (sn-1, 2 or 3) will dictate their
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physical properties, digestibility and impact on human health. TAG digestion and absorption are complex processes and involve a number of physicochemical
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events along the GIT. Following ingestion of fats or oils, the first step in TAG absorption is
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hydrolysis in the mouth and stomach where they are hydrolyzed by lingual and gastric lipases that preferentially hydrolyze the sn-3 position of TAGs to generate fatty acids in their free form [(free fatty acidsFFAs)] or non-esterified fatty acids (NEFAs) and 1,2-diacylglycerols [13-15]. In healthy adults, there occurs ~ 10-30 % lipolysis of ingested TAGs in the stomach [16, 17]. The ensuing step is further TAG breakdown in the duodenum where pancreatic lipase adsorbs onto the surface of pre-existing oil droplets, or those formed in-situ by interacting with adsorbed bile salts and other surfactants in the stomach and small intestine. Pancreatic lipase preferentially 4
ACCEPTED MANUSCRIPT hydrolyzes the sn-1 and sn-3 position in TAGs [15], leading to the formation of FFAs and 2monoacylglycerols (2-MAGs). The third step involves solubilization and uptake of lipolytic products by the enterocytes, which are then encapsulated in self-assembled structures, such as bile salt micelles and phospholipid vesicles and transited to intestinal epithelial cells for
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absorption [18]. These self-assembled structures increase the aqueous concentration of lipolytic
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products, which enhances their absorption rate. In the last step, long-chain FFAs (long-chain: >
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12C and very long-chain: ≥ 20C) and 2-MAGs are transported into the endoplasmic reticulum inside the enterocytes, where they are re-synthesized into TAGs [19-21]. These TAGs are
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packaged with cholesterol, lipoproteins and other lipids into chylomicrons that are distributed to
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different cells via the lymphatic system and then onwards to systemic circulation [22]. By contrast, short- (< 6C) and medium-chain (6C - 12C) FFAs are transported bound to serum
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albumin and leave the enterocytes through the portal vein [20].
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Internationally, the agri- food sector is in the midst of undergoing a revolution where food is no
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longer simply seen as a low- margin commodity. Rather, it is increasingly being seen as source of improved health and increased revenue potential. For example, the introduction of healthier food
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options by agri- food manufacturers is resulting in greater sales, thus benefiting margins further
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as health-conscious consumers generally pay more for foods that they believe is healthy for them. According to a global health and wellness report of 30,000 people, 90% of consumers are willing to pay more for foods with added quality and benefits [23]. In this context, judicious control of lipid digestion opens up the possibility of developing new food products with added health benefits such as controlled lipid bioaccessibility and release of specific fatty acids from food fats and oils within the GIT. As a result, deliberate control of food structure for controlled
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ACCEPTED MANUSCRIPT lipid delivery is an area of rapidly- growing research. In this review, we identify some of the latest research trends in lipid digestion and the implicit role played by food structure design.
2. Dietary TAGs
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The fatty acid distribution within naturally-occurring TAGs is not random [24, 25]. The
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taxonomic patterns of vegetable oils consist of TAGs obeying the 1, 3-random-2-random distribution, with saturated fatty acids being located almost exclusively at the 1, 3-positions of
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TAGs [26]. Conversely, fats from the animal kingdom (tallow, lard ) are quite saturated at the sn-
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2 position [27].
In describing the physical properties of food lipids, one must consider whether they are in the
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liquid or solid state. At room temperature, processed oils will be liquid whereas fats will be
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solid- like. Compositionally, oils will primarily consist of mono or poly- unsaturated fatty acids whereas fats will be generally much higher in saturated fatty acid content. Along with the degree
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of unsaturation, the extent to which neighbouring fatty acids interact both intra- and inter-
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molecularly will dictate whether a TAG exists in the liquid or solid state [28]. During crystallization, TAG molecules adopt a “tuning- fork” or “chair” conformation with, for example,
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the sn-2 fatty acid pointing in the opposite direction to the sn-1 and sn-3 fatty acids, which results in the formation of distinct TAG crystalline lamellae that assemble into a fat crystal network [29]. Once crystallized, TAGs have different packing modes known as the α, β′ and β polymorphic forms, each with a distinct melting point [30]. For example, the melting point of tristearin (a triester of stearic acid) in the α, β′ or β form is 54, 64 and 73 °C, respectively [31]. Common fats used in processed foods include butter (milk fat), beef fat, chicken fat, pork fat (lard, bacon), stick margarine, and shortening. 6
ACCEPTED MANUSCRIPT Interesterification, hydrogenation, and fractionation are three processes available to food manufacturers to tailor the physical, and chemical properties of food lipids. Each operation is based on different principles to attain its goal. Fractionation is a physical separation process based on the distinct crystallization temperature of different TAGs; thus, crystallization at a set
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temperature is used to separate TAGs that have solidified from those tha t remain liquid.
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Hydrogenation is a chemical process leading to the saturation of double bonds present in fatty
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acids in the presence of hydrogen gas and a metal catalyst to harden fats for use as margarine and shortening base stocks, but also potentially results in the formation of trans unsaturated fatty
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acids [32]. The usage of hydrogenated fats is declining due to the negative health effects (e.g.,
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heart disease) of hydrogenated fats enriched in trans fatty acids and governmental pressures to reduce trans fat levels in food products [33, 34]. Finally, interesterification causes a fatty acid
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redistribution within and among TAGs, which can lead to substantial changes in lipid
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functionality, such as melting point or profile [32]. Fractionation and/or interesterification are common unit operations for the production of a low or “zero-trans” fats with desirable physical
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properties (e.g., a higher melting point).
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2.1. Emulsified oils and fats
In processed foods, the vast majority of fats and oils are present as emulsions. Contrary to bulk
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fats, emulsions consist of two immiscible liquids with one phase dispersed within the other as droplets. In foods, most emulsions consist of oil droplets dispersed in a continuous aqueous phase, such as a vinaigrette where vegetable oil is dispersed as droplets in a vinegar solution. To create such oil- in-water (O/W) emulsions, it is necessary to supply energy in order to subdivide the oil into micron-sized dispersed droplets within the continuous vinegar phase, which is usually achieved by high- intensity agitation. Emulsifiers such as proteins and small- molecule surfactants
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ACCEPTED MANUSCRIPT such as lecithin are used to emulsify and coat the dispersed oil droplets, which slows their separation [35]. Over time, all emulsions will separate into oil and aqueous layers, via mechanisms such as creaming, flocculation and coalescence [36]. Creaming is a separation process based on density
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differences between food oils and water, which results in the formation of an oil layer atop an
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aqueous layer, as is observed in freshly-produced milk [35]. With flocculation, two or more oil
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droplets will aggregate with one another while remaining intact [37, 38]. This step is a precursor to coalescence where flocculated droplets merge to form a single larger droplet. In practice,
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careful emulsifier composition and concentration will ensure that food emulsions remain stable
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against coalescence during their expected shelf life [39], which can range from minutes in the case of home- made vinaigrette to years in the case of mayonnaise. Emulsion breakdown in the
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human gut also depends on the choice of stabilizing surfactant or protein as these can greatly
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affect the extent and rate of oil droplet coalescence. As further described below, coalescence reduces oil droplet surface area, which slows the rate of fat digestion by the body, potentially
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impacting fat absorption and release of GIT hormones, such as those associated with satiety. As
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emulsions represent the dominant form in which fats and oils are found in natural and processed foods, this review focuses on the fate of emulsified fats and oils dispersed in different food
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matrices. We demonstrate that the properties of emulsions and the surrounding food matrix both play important roles in modulating the digestion of food fats and oils.
3. Disintegration of foods in the GIT The GIT is the anatomical ‘tube’ that extends from the mouth to the anus, including organs responsible for transit, digestion and absorption of foods. Food assimilation occurs in the upper 8
ACCEPTED MANUSCRIPT GIT, namely the mouth, esophagus, stomach and small intestine. The mouth, defined as the hollow space between the lips and the velum [40], namely contains teeth, the tongue and salivary glands. The stomach is a J-shaped enlargement of the GIT that connects the esophagus and duodenum. It is made up of four parts: the cardia, fundus, body and pylorus [41]. Antral
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contraction waves (3 cycles min-1 ) proceed from the body of the stomach towards pylorus,
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resulting in food mixing, antral grinding and gastric emptying [42]. Gastric juice containing
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pepsin and hydrochloric acid is secreted by gastric glands, with the fasting gastric pH being 1.52.0 [43, 44]. The small intestine is made up of the duodenum, jejunum, and ileum, and is where
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digestion is completed. Bile and pancreatic juices are secreted into the duodenum [41]. The pH
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of gastric chyme (which consists of partially-digested food and digestive juices) reaches 6-7 in the duodenum after mixing with intestinal juices [44]. Throughout the length of the small
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intestine, the mucosa is lined with enterocytes covered by villi and microvilli that enhance
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nutrient absorption, which mainly occurs in the duodenum and jejunum [41].
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During digestion, foods continuously interact with the GIT. The initial shape and structure of a food is modified by dilution, digestive enzymes, mechanical shearing/grinding, and changes in
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pH and ionic conditions. As a highly-dynamic process, an understanding of food breakdown in
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the human body is clearly important for food product development and nutritional assessment. As in vivo human trials, though powerful in outcome, are sometimes limited by ethical constraints [45], in vitro models that simulate the GIT are seeing increased usage to easily probe digestive phenomena. Although it remains impossible to perfectly simulate physiological conditions, in vitro digestion can provide useful information associated with in vivo processes such as fatty acid release from dispersed fats and oils [45].
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ACCEPTED MANUSCRIPT Food disintegration includes three stages: oral processing, gastric digestion and intestinal digestion. In the mouth, humans are predisposed to different patterns of food oral processing (e.g., number of chewing cycles and duration of mastication) based on the properties of the foods [40, 46]. Mastication breaks down a solid food into small particles and mixes it with saliva to
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form a cohesive bolus ready for swallowing whereas liquid foods stay in the mouth for seconds
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and are swallowed directly [40]. In general, the degree of fragmentation of solid foods increases
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with increasing food hardness [47]. Though mastication, mixing with saliva, and the friction between oral surfaces will break foods down into milli-scale particles, their microstructure will
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liquid emulsions such as salad dressings [48-51].
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remain largely intact, whether we speak of solid foods such as nuts, spaghetti, or protein gels or
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In the stomach, proteins are significantly hydrolyzed by pepsin whereas lipids are only partially digested and carbohydrates see little breakdown [41]. Larger post-oral processing food particles
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are further broken down into smaller particles (< 1-2 mm) by antral grinding [52], which along
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with gastric juices, results in significant disruption of food microstructure. Destabilization of O/W emulsions occurs during gastric digestion, the degree of which depends on the nature of
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interfacial film covering the dispersed oil droplets and the food matrix surrounding the oil
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droplets [53, 54]. During gastric processing, larger oil droplets (e.g., > 6 μm) may coalesce, cream and phase-separate in the stomach, which affects their rate of gastric emptying and ensuing digestion in the small intestine [55, 56]. However, as oil droplets are often dispersed within complex structures such as cheese and sausages, most of them may not be released at all during gastric digestion. In the small intestine, most food macronutrients are physically and chemically broken down with the aid of a series of enzymes, such as trypsin, chymotrypsin, pancreatic lipase, colipase, and α10
ACCEPTED MANUSCRIPT amylase, which facilitates their absorption [41]. Both pre-existing emulsified oils and fats or emulsions formed in-situ in the duodenum or the stomach must be exposed to the intestinal environment for hydrolysis and uptake [16, 53, 55, 57]. Together, the interfacial film and the food matrix surrounding the dispersed oil droplets as well as the composition of the oil and fat
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will modulate their intestinal digestion (Figure 2).
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The following sections highlight the influence of interactions between the GIT and model or real
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foods on lipid digestion, with a focus on the relationship between food structure and lipid digestion. We define model systems as foods with a controlled degree of complexity vs.
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naturally-occurring or processed foods which are inherently more complex given their greater
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4. Role of TAG composition on digestion
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number of co-existing, interacting ingredients and phases (liquid, solid and gas).
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TAG composition greatly affects many properties of oils and fats, such as melting point, solid fat content (SFC), crystal structure and the FFA types released during digestion. As a result, TAG
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composition is an important factor that should be considered in designing foods containing oils
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and fats. 4.1. TAG composition
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Fatty acid chain length and degree of unsaturation along with their positional distribution may impact TAG rate and extent of lipolysis. Furthermore, if TAG molecule s contain a polar group (e.g., phosphate group), there will be a significant effect on lipolysis. The rate and extent of TAG digestion during in vitro digestion will decrease with increasing fatty acid chain length in this order: short-chain triacylglycerol (SCT) > medium- chain triacylglycerol (MCT) > long-chain triacylglycerol (LCT) [58-61]. This is ascribed to the fact that FFAs released from LCTs can
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ACCEPTED MANUSCRIPT accumulate at oil droplet surfaces, thereby restricting easy lipase access to other TAGs [62, 63]. By contrast, medium or short-chain FFAs have a higher affinity for water and rapidly move into the surrounding aqueous phase after formation, making it easier for the lipase to hydrolyze as- yet unaffected TAGs [64]. However, this effect of long-chain FFAs delaying lipid digestion is
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dependent on bile concentrations as higher bile salt concentrations result in a higher rate and
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extent of LCT digestion [62, 65-67]. By contrast, the digestion of MCT is not dependent on bile
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salt concentrations [64].
The positional distribution of fatty acids on TAG molecules can be modified using
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interesterification, thereby influencing lipid digestion. For example, in a mixed system with
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structured oils containing both medium-chain fatty acids (M) and linoleic acid (L), Nagata et al. found that in vitro TAG hydrolysis by pancreatic lipases was 2–3- fold higher for MLM vs. LML
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TAGs, with the corresponding serum TAG levels higher in rats fed MLM type vs. LML. This
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confirmed that the positional distribution of fatty acids within TAGs (especially long-chain fatty acids at the sn-1 or sn-3 positions) affected lipid digestion [59]. Interestingly, soybean oil (an
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LCT) and coconut oil (an MCT) showed similar bioavailability (97 – 99 %) in an animal study,
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suggesting the need for further studies in this area [68]. The degree of unsaturation of TAGs (i.e., poly vs. mono- unsaturation) does not appear to
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significantly affect lipid digestion, though work remains to be done in this area. Of the scarce reports available, Zhang et al. and Ozturk et al. reported that the fish oil emulsions containing very long-chain polyunsaturated fatty acids (e.g., eicosapentaenoic acid and docosahexaenoic acid) showed FFA release profiles similar to corn oil emulsions, which are rich in oleic acid, which is monounsaturated, and linoleic acid, which contains two double bonds [61, 69].
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ACCEPTED MANUSCRIPT Dietary phospholipids, a major component of membrane lipids, have an amphipathic structure with hydrophobic properties conferred by the fatty acid chains at the sn-1 and sn-2 positions and hydrophilic properties conferred by the sn-3 phosphate group. Dietary phospholipids can affect lipid digestion and absorption through different mechanisms [22, 70]. For example, pancreatic
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phospholipase A2-knockout mice were shown to be resistant to high- fat diet- induced obesity
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[71], perhaps due to the limited release of MAGs and lysophosphatidylcholine (as surfactants)
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given that the lack of phospholipase can lessen the ability of bile salts to form mixed micelles
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that remove lipolytic products from the oil-water interface during digestion [22]. Phospholipids are critical for dietary lipid absorption [72]. The remodeling enzyme
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lysophosphatidylcholine acyltransferase 3 (LPCAT3) is an enzyme that modulates membrane
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phospholipid composition [73]. A recent study showed reduced plasma TAG levels were observed in intestine-specific LPCAT3 knockout (IKO) mice [72]. By contrast, administration of
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16:0/20:4 phosphatidylcholine to IKO intestines increased fatty acid uptake to a level
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comparable to control intestines, implying phospholipids played an important role in lipid passive absorption through the membrane of enterocytes.
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4.2. Physical state – oil vs. fat
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The physical state of fats and oils can significantly impact their digestibility. It was recently shown in an in vitro study that emulsified fats with a higher SFC were less susceptible to lipolysis than their lower-SFC counterparts [74], likely as result of pancreatic lipase access to TAGs being more limited at higher SFC. In vivo animal and human studies have also both shown that TAGs in the solid state have a much lower bioavailability than liquid TAGs [55, 68, 75]. Interestingly, O/W emulsions prepared using rapeseed oil (which is liquid) resulted in much lower hunger ratings than emulsions containing hydrogenated palm fat (which is a hard fat) in a 13
ACCEPTED MANUSCRIPT double-blind, randomized and crossover-designed human trial, probably due to the slow digestion and lower bioaccessibility of the palm fat rather than differences associated with the constituent fatty acids [55].
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5. Interfacial structure of food emulsions and lipid digestion
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An O/W emulsion consists of emulsified lipids dispersed as droplets within a continuous aqueous phase. The interfacial film at the droplet surface is key in determining emulsion stability
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and digestibility. Key factors dictating the properties of interfacial films include surface charge, film thickness, and surface activity, which can all greatly impact susceptibility to enzymatic
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attack.
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5.1. Emulsifier types
Proteins, polysaccharides and small- molecule surfactants are widely used in food applications.
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Proteins can form an interfacial film on the surface of droplets whose properties are influenced
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by the surface charge and hydrophobicity of constituent amino acids and their 3D rearrangement following interfacial adsorption [76]. Some polysaccharides possess surface activity that
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originates from either the non-polar chemical groups attached to the hydrophilic polysaccharide
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backbone (e.g., modified cellulose) or the presence of a protein moiety covalently or physically linked to the polysaccharide (e.g., pectin) [77]. Small- molecule surfactants are much smaller but much more surface-active than proteins and polysaccharides, and decrease surface tension to a larger extent, which typically results in emulsions with a lengthier kinetic stability under quiescent conditions [76]. The digestion of protein-stabilized emulsions as affected by protein structural and biochemical factors has been summarized in a previous review [53]. Nominally, a protein film present at an 14
ACCEPTED MANUSCRIPT oil- water interface will be easily broken down by proteases and displaced by bile salts [78]. Protein properties generally have little effect on lipid digestion, though this is highly dependent on protein type [53]. Compared with animal proteins, interfacial films formed by plant proteins may provide enhanced protection against lipolysis during digestion. For example, as the
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insolubility and hydrophobicity of deamidated wheat gliadins are much higher than dairy
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proteins [79], they form a more compact interfacial film that is resistant to displacement by bile
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salts. This hinders the diffusion of lipase towards oil droplet surfaces, resulting in a lower extent of lipid digestion [80]. Similarly, soybean proteins are more resistant than β- lactoglobulin (β- lg –
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a dairy whey protein) to interfacial displacement by bile salts at the oil-water interface [81],
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leading to the delayed lipid digestion [82], the cause being their two different fractions that differ greatly in structure from β- lg: a hydrophilic polysaccharide that is esterified to a polypeptide [83].
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The former protects the emulsion droplet surface by forming a thick hydrated layer whereas the
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latter is anchored into the oil droplet core.
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Most polysaccharides are used to thicken foods as they have little propensity towards emulsification, given their lack of surface activity [77]. Other polysaccharides, such as gum
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Arabic, modified starches, modified celluloses, pectin, and galactomannans, show some
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surface/interfacial activity [84]. Although the emulsification capacity of polysaccharides is not efficient compared to proteins and small- molecule surfactants, they can form a thicker interfacial film around dispersed oil droplets. For examples, hydroxypropyl methylcellulose (HMPC) is a chemically modified cellulose with a high molecular weight (100 000 g·mol-1 ) used in foods as a thickener, bulking agent, fibre source and emulsifier. At oil droplet surfaces, its adsorbed layer is several hundreds of nanometres thick, which is much greater than that of protein layers (1-10 nm) [85, 86]. When present in emulsions, low concentrations of bile salts will disrupt, though not
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ACCEPTED MANUSCRIPT completely displace, HMPC adsorbed to an oil- water interface [82, 87-89]. In this case, retarded lipolysis is mainly attributed to the binding between bile salts a nd any unadsorbed HMPC present in the emulsion’s aqueous phase [89]. Finally, food- grade surfactants (e.g., lecithin, phospholipids and polysorbates), though widely
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used in processed foods, play a limited role in modulating in vitro lipid digestion as they are
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easily displaced by bile during digestion [70, 90-95]. 5.2. Adsorbed multilayers
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Multilayers are produced by attaching alternating layers of oppositely-charged biopolymers onto emulsion droplets using layer-by- layer deposition. To do so, an O/W emulsion is initially
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stabilized by a charged water-soluble emulsifier such as most proteins or lecithin. Afterwards, an
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oppositely-charged biopolymer such as chitosan, gum Arabic, carrageenan, pectin and chitosan is deposited under different pH and ionic strength conditions. This process is repeated until the
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desired number of multilayers is attained. Such multilayers are thought to confer more protection
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against lipolysis than a monolayer. However, pH plays a huge role in this eventuality. After food ingestion, the pH in the stomach decreases from 5 – 6 to 1.5 – 2.0 [96, 97], whereas the pH of
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chyme increases to ~ 6 - 7 after entering the duodenum and mixing with intestinal juices [41]. As
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the interaction between anionic and cationic biopolymers is pH-dependent [98], the large variations of pH in the GIT will greatly affect multilayer stability [99], which will subsequently impact dispersed oil digestibility [100-102]. 5.3. Solid particles and solid interfacial shells Compared with molecular emulsifiers, micro or nano-scale particles can anchor to the oil-water interface with a very high desorption energy that renders them virtually irreversibly attached [103]. As a result, they limit the ability of bile salts and enzymes to physically contact the 16
ACCEPTED MANUSCRIPT surface of dispersed oil droplets, leading to a decreased extent of digestion. For example, Sarkar et al. formed whey protein microparticles through homogenization of a heat- induced 10% whey protein isolate gel [104], showing that these emulsions were stable during in vitro gastric digestion resulting in delayed lipid digestion during subsequent intestinal digestion compared
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with a control whey protein-stabilized emulsion. In general, if digestible, particles whether
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carbohydrate, fat or protein-based, will show a limited ability to retard the digestion of
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emulsified lipids [105, 106]. By contrast, non-digestible particles can greatly suppress lipid digestion. As an example, nanocrystals based on chitin, an abundant natural amino-
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polysaccharide [107], can significantly retard the rate and extent of lipid digestion compared to
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protein-stabilized emulsions, given their insolubility, lack of digestibility, and strong adsorption
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to the oil-water interface [108].
An alternative approach that may delay lipid digestion consists of using thermosensitive species
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such as starch granules, which can form continuous solid shells around dispersed oil droplets.
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For example, Sjöö et al. exposed O/W emulsions stabilized by starch shells to simulated GIT conditions and showed that the extent of lipid digestion was lowest when the starch had
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gelatinized enough to create a dense layer around the oil droplets but hadn’t swollen into a
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porous structure that granted access to the lipase [105, 109].
6. Food gel matrix and lipid digestion When oil droplets are dispersed in a solid-like food matrix (e.g., cheese or yogurt), the structure of the surrounding food matrix becomes the dominant factor controlling digestion [110]. During digestion, the 3D network structure within a food matrix (i.e., the spatial architecture resulting from the assembly of macromolecules such as proteins, polysaccharides and lipids into a 17
ACCEPTED MANUSCRIPT coordinated network) can obstruct the diffusion of enzymes towards the surface of dispersed oil droplets. Compared to interfacial films, the solid like-food matrix is potentially capable of providing enhanced protection against lipolysis. A broad range of processed food products, including yogurt, cheese, some sauces, and
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reformulated meat products consist in part of such p rotein-based emulsion gels [110]. As a
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model system, a number of studies have investigated the role of the structure of whey protein
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emulsion gels on lipid digestion [48, 54, 74, 97, 111-113]. In these studies, gels with different microstructures were formed by heating whey protein emulsions containing sub-micron oil
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droplets in the presence of different salt concentrations, which was a necessary conditions for
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gelation [48, 112]. Softer gels containing lower NaCl concentrations (< 50 mM) consisted of a homogeneous protein matrix while harder gel produced at higher NaCl concentrations (> 100
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mM) consisted of a porous protein network (Figure 3A). This difference in gel microstructure
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was an important contributor to differences in dispersed oil digestion. During in vivo mastication, few oil droplets were released from both hard and soft gels (Figure 3B) [48, 112]. During gastric
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digestion, however, the soft gel rapidly dissolved whereas the hard gel only broke down in
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smaller particles, and showed limited oil droplet release (Figure 3C) [48, 54, 97]. Finally, during intestinal digestion, the soft gel presented a digestion behaviour similar to a liquid whey protein
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emulsion whereas remnants of the hard gel remained, thereby leading to a lower lipolysis rate (Figure 3D) [113].
In another example, emulsion-filled hydrogel beads consisting of alginate or κ-carrageenan were resistant to disintegration during oral, gastric and intestinal digestion [114-116]. Here, the digestion of oil droplets within the beads was greatly delayed compared to free oil droplets. This largely resulted from the hydrogel matrix restricting the diffusion of lipase to the surfaces of oil
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ACCEPTED MANUSCRIPT droplets, the presence of electrostatic interactions between the biopolymers and pancreatic lipase at neutral pH and the non-digestibility of the biopolymer mixture. By contrast, a rice starchbased gel was shown ineffective at protecting incorporated oil droplets against hydrolysis [117],
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due to its low gel strength, swelling and high digestibility [105, 118-120].
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7. Effect of oil droplet size on lipid digestion
In vitro digestion studies have shown that the original droplet size of an emulsion and the change
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in droplet size during digestion greatly influence the rate of lipid digestion, namely that a larger droplet size will almost invariably result in a lower rate of digestion [121-125]. In general, oil
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droplet size increases upon gastric and intestinal digestion due to flocculation and coalescence,
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though this highly depends on the original size and surface properties of the oil droplets [126,
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127].
Recently, the gastric emptying, creaming and phase separation of acid-stable and acid-unstable
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O/W emulsions were investigated using magnetic resonance imaging [128]. This study showed
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that acid-stable emulsions largely retained their gastric stability throughout the 180- min scanning period and their duodenal contents were homogeneous. By contrast, acid-unstable emulsions
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underwent structural changes with evidence of fat phase creaming and droplet flocculation, and as a result were emptied more quickly from the stomach than the acid-stable emulsions. In another study, Armand et al found that both fine (0.7 μm) and coarse (10 μm) acid-stable emulsion droplets stabilized by lecithin and dairy proteins were relatively stable in the human stomach based on the small change in oil droplet size observed with time [17]. As well, Steingoetter et al. reported that a reduction in droplet size by 2 orders of magnitude (0.3 vs. 52 µm) delayed gastric emptying by 38 min for acid-stable emulsions in a human trial [55]. These in 19
ACCEPTED MANUSCRIPT vivo human studies demonstrate that the gastric stability and particle size of food emulsions greatly affects the transit of emulsified oils and fats in the GIT and may further influence lipid digestion, which needs to be considered when formulating foods.
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8. Lipid digestion in natural and processed foods
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In ‘real’ food products, lipids are dispersed within a liquid or solid food matrix which is normally more complex and heterogeneous than the model systems discussed above. In the
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context of this review, it is therefore pertinent to pose a question: Can novel approaches to modulating lipid digestion in real food products be achieved on the basis of knowledge of
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digestion in model foods? Some evidence in support of this view is briefly presented below for a
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number of cases: almonds and almond milk, bovine and human milk, infant formula and firm cheese.
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8.1. Almonds
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Almonds are a valuable dietary source of lipids, proteins, dietary fibre, vitamins, minerals, phenolic compounds and phytosterols. Their structure is representative of many nuts and seeds
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(e.g., walnut, peanut and sesame seed). Oil bodies, which are the oil-bearing structures that may
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represent over 50 % of the nut weight, are located within thin-walled cells (Figure 4) [129]. Intra-cellular lipid bodies are ∼1-3 μm in diameter and stabilized by a monolayer of phospholipids and oil body-specific proteins mostly from the oleosin family [130]. The release of oil bodies from almond cells or the diffusion of lipase towards these cells is necessary for lipolysis. Approximately 10% of lipids in raw and roasted almonds have been observed to be released from almonds upon mastication with the cells remaining largely intact [49]. The particle size of 20
ACCEPTED MANUSCRIPT whole almonds in another study decreased to 500 and 350 μm for raw and roasted almonds, respectively, after mastication and in vitro gastric digestion [131]. The rate and extent of lipid digestion of almond cells were much lower than that of the isolated o il bodies (22 vs. 69% hydrolysis after 1 h digestion) during in vitro intestinal digestion [132]. In vitro digestion studies
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are highly consistent with in vivo human trials. Berry et al. found that the postprandial increase in
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plasma TAG levels was lowered by 74% after whole almond meal consumption vs. almond flour
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[11]. In another study, a large proportion of cells remained intact and undigested oil bodies were found in faeces after consumption of an almond diet [133]. From in vitro oral to duodenal
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digestion, no significant changes were observed in the cell wall composition of almonds [131].
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Intact almond cells retained their intracellular lipids even after long periods of digestion (20 hours), and encapsulated lipids contained in intact almond cells could only be digested by lipases
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that slowly diffused through to the cell wall [132]. However, lipases easily penetrated the cell
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wall of damaged cells to access intracellular lipids [132]. Therefore, the digestion and bioaccessibility of lipids in almonds was regulated by the structure and properties of the cell
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walls surrounding the oil bodies.
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Due to the low bioaccessibility of TAGs in whole almonds, oil bodies are often studied after their
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extraction and resuspension in an aqueous environment to form a milk [134]. When oil bodies are released from the cells, the protease and lipase can easily access their surface to then hydrolyze the incorporated TAGs. Digestion of such oil bodies has been recently studied both in vitro and in vivo, where it was shown that an almond oil body emulsion behaved similarly to a protein-stabilized O/W emulsion in a simulated GIT environment [135]. An in vivo animal study showed that almond milk tended to coalesce under gastric conditions, which differed from in vitro digestion [135, 136], suggesting that gastric lipase, which was absent in the in vitro study, played an important role in lipid
21
ACCEPTED MANUSCRIPT digestion. Overall, these results demonstrate that both the interfacial structure of emulsion droplets and that of the surrouding matrix play a preeminent role in dispersed oil digestion. 8.2. Milk and infant formula Milk is a complex food emulsion consisting of ~ 3 - 4 μm fat globules, various proteins and
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carbohydrates dispersed in an aqueous serum [137, 138]. Native milk fat globules are stabilized
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by a lipid trilayer rich in integral and peripheral proteins in the milk fat globule membrane
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(MFGM) [138, 139]. Thermal treatments such as pasteurization are commonly used to destroy
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potential pathogens, allowing for safe consumption and a long shelf life. Such thermal treatments also result in denaturation of some MFGM proteins, aggregation of milk serum proteins and
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interactions between the MFGM and these proteins, thereby influencing milk digestion [140,
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141]. De Oliveira et al. compared the kinetics of in vitro lipolysis of raw versus pasteurized human milk from a donor milk bank at the University Hospital Centre in Rennes, France [141].
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After 60 min of gastric digestion, more severe flocculation and aggregation occurred in raw milk.
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By contrast, there was no large variation in the particle size distribution of pasteurized milk during gastric digestion, which appeared related to the protective effect of pasteurization- induced
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protein aggregates adsorbed at the surface of fat globules. The gastric lipolysis rate of
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pasteurized milk was also significantly lower than that of raw milk, which was ascribed to inactivation of bile salt-stimulated lipase (BSSL) (an endogenous lipase of human milk) by pasteurization and, as above, protection by adsorbed protein aggregates. By contrast, a n animal study showed that pasteurization did not greatly affect gastric lipolysis of bovine milk (origin: pasture-raised Friesian cows on a dairy farm in Palmerston North, New Zealand) where BSSL is absent [142]. This suggests that BSSL plays an important role in the lipid digestion of human milk during gastric digestion. In a randomized controlled human trial, pre-term infants were fed
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ACCEPTED MANUSCRIPT raw or pasteurized milk collected from their own mothers to evaluate the effect of pasteurization on milk digestion [143]. In the stomach, the specific surface area of milkfat globules in pasteurized milk was larger than that of raw milk, however their rates of lipolysis showed no difference, strongly suggesting enhanced protection by heat- induced structural changes in human
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milk protein. Other studies have shown that changes in MFGM surface composition induced via
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homogenization do not significantly affect lipolysis compared with raw milk [144, 145]. Finally,
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in a comparative study on infant formula and human milk, the extent of lipid digestion between the two was no different [146, 147], even though vegetable oil droplets in infant formula were 10
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x smaller than milkfat globules in mother’s milk (~ 0.4 vs ~ 4 μm). This suggested that the
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MFGM was more susceptible to digestion than typical interfacial protein layers surrounding vegetable oil droplets [146]. Such studies demonstrate the need for further research that fully
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addresses the role of interfacial structure on lipolysis in infant formula and associated products.
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8.3. Cheese
Processed dairy products like cheese and yogurt are food emulsions with oil droplets
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incorporated within a solid or semi-solid matrix. Processing steps such as heating applied to
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make these products greatly influence the structural characteristics and the properties of the protein matrix, which will largely determine product disintegration, diffusion of digestive
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enzymes into the matrix, and nutrient release. Studies have shown that peptides and FFAs are more easily released from milks and yogurts (which are liquid and semi-solid matrices, respectively) vs. cheeses (which are solid matrices) owing to easier breakdown of the food matrix and greater accessibility by digestive enzymes in the former two [148, 149]. Yogurts have shown similar proteolysis and FFA release kinetics to fluid milk likely due to the formation of soft clots by milk protein during gastric digestion [150-
23
ACCEPTED MANUSCRIPT 152]. For cheese, the structural characteristics and hardness are determinants of lipid digestion. Fang et al. compared the disintegration and lipolysis of cheeses with different textural properties [153], and found that regular Cheddar cheese had a significantly higher extent of lipid digestion than light Mozzarella cheese. The larger fat globules in Cheddar cheese acted as weak points in
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its microstructure and texture, which led to a greater decrease in hardness and greater
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disintegration during in vitro digestion. By contrast, light Mozzarella consisted of a denser
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fibrous protein matrix due to the stretching step that occurs during its fabrication. Its protein matrix showed a lower rate of disintegration and protein hydrolysis, thereby provid ing enhanced
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protection to dispersed fat and hence a lower extent of digestion [153]. The presence of calcium
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in cheese plays a significant role on texture and structure. Ayala-Bribiesca et al. found that addition of calcium to Cheddar cheese during production greatly increased its firmness, and
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decreased its disintegration rate during digestion, but enhanced lipid digestion [154]. They
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ascribed this behaviour to the formation of calcium soaps of long-chain fatty acids that helped remove FFAs from the oil- water interface as well as the higher degree of fat aggregation it
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induced [62].
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These various examples show that the properties of emulsified lipids and the surrounding matrix
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can significantly change the rate and extent of lipid digestion, strongly supporting the concept of food structure design as a tool to modulate lipid digestion in foods.
9. Concluding remarks and future directions Food structure design may be used as a tool to develop foods that permit control over the location, extent and rate of release of food fats and oils within the GIT. As most studies on this topic have been carried out using a simulated GIT environment, further validation of novel 24
ACCEPTED MANUSCRIPT approaches to controlling lipid digestion in processed foods requires in vivo human trials to fully understand the digestion and fate of emulsified lipids in real food products. Doing so will help decipher the relationship between dietary fat composition and structure on physiologic mechanisms regulating lipid digestion and absorption as well as outcomes such as enhanced
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satiety via the ileal brake in test populations [6, 12, 155-157]. Moving forward, food structure
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design should continue to play an increasingly important role in the development of foods where
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CE
PT
ED
M
AN
US
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targeted health benefits are desired.
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ACCEPTED MANUSCRIPT Figure captions
Figure 1 Some structural elements in foods and relevant length scales. Redrawn with permission
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Figure 2 Simplified schematic of emulsified lipids in a food matrix.
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[7].
Figure 3 Structural changes in a firm whey protein emulsion gel containing small oil droplets
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during in vitro digestion. The red colour represents oil droplets and the green colour represents
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proteins. A, B, C and D represent the original gel, gel bolus, gastric digesta at 60 min, and
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magnification (larger scale bar).
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intestinal digesta at 90 min, respectively. Fragments of the gel bolus are shown at the low
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Figure 4 Transmission electron micrograph image of almond kernel showing oil bodies (grey
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[129].
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inclusions), protein bodies (black inclusion) and the cell walls. Reproduced with permission
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