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Fat taste and lipid metabolism in humans
Physiology & Behavior 86 (2005) 691 – 697
Fat taste and lipid metabolism in humans Richard D. Mattes * Purdue University, Department of Foods and Nutrition, 700 W State Street, W. Lafayette, IN 47907-2059, USA Received 12 July 2005; accepted 25 August 2005
Abstract Dietary and body fat are essential for life. Fatty acids modulate fat detection, ingestion, digestion, absorption and elimination. Though direct effects occur throughout the body, much of this regulation stems from signals originating in the oral cavity. The predominant orosensory cue for dietary fat is textural, but accumulating electrophysiological, behavioral and clinical evidence supports olfactory and gustatory components. Orosensory stimulation with long-chain unsaturated, but possibly also saturated, fatty acids elicits an array of cephalic phase responses including release of gastric lipase, secretion of pancreatic digestive enzymes, mobilization of lipid stored in the intestine from the prior meal, pancreatic endocrine secretion and, probably indirectly, altered lipoprotein lipase activity. Combined, these processes influence postprandial lipemia. There is preliminary evidence of marked individual variability in fat ‘‘taste’’ with uncertain health implications. The possibility that fat taste sensitivity reflects systemic reactivity to fat warrants further evaluation. D 2005 Elsevier Inc. All rights reserved. Keywords: Cephalic phase; Lipid; Fat; Taste; Smell; Texture; Chemosensory; Triacylglycerol; Fatty acid; Human
Despite two decades of fat vilification by the health care community and media, absolute intake of fat changed little and consumption remains high and is now growing [1]. A common argument for such a strong defense of fat intake is that the nutrient has provided some adaptive value. While associations with chronic diseases dominate current thought, the beneficial effects are diverse and multiple. Fats are: i) integral components of cell membranes, influencing their structure and function; ii) precursors for eicosinoids that regulate blood clotting, blood pressure and immune function as well as hormones critical for reproductive function (e.g., estrogens, testosterone) and bone health (calcitriol); iii) a carrier for fat soluble vitamins; iv) a thermal insulator; v) a shock absorber; vi) an energy substrate and vii) a source of sensory stimulation. Consequently, it is plausible that mechanisms evolved to promote fat intake. One potential mechanism is an orosensory capability to detect dietary fat coupled with a positive hedonic impression. This system may take several forms. First, the sensory impression could be inherently appealing. Second, orosensory detection initiates neurally mediated physiological
* Tel.: +1 765 494 0662; fax: +1 765 494 0674. E-mail address: [email protected]. 0031-9384/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.physbeh.2005.08.058
responses (cephalic phase responses) that reinforce ingestion [2]. Third, the metabolic feedback following actual ingestion of such an energy dense substance is rewarding [3,4]. Recently, evidence has emerged that fatty acids are ‘‘tasted’’ in post-oral regions of the GI tract and in the periphery with implications for ingestion. The term ‘‘taste’’ is used for sensing fatty acids outside the oral cavity because taste transduction mechanisms reportedly present in the oral cavity for fatty acids are ubiquitous. For example, delayed rectifying potassium channels linked to fat detection by oral taste receptor cells are also present in the intestine, pancreas, liver and heart [5,6]. The fatty acid transporter protein, CD36, is located on oral taste receptor cells as well as in the intestine, adipose tissue, skeletal muscle, heart and brain [7– 12]. Within the intestine, CD36 mediates the release of hormones linked to appetite such as CCK [13] and PYY [14]. While the biophysics of these transduction mechanisms is common, the effects vary markedly with site and may provide an integrated system for the control of fat intake and metabolism [15 –18]. For example, dietary lipid in the mouth may promote ingestion while its later presence in the intestine alters gustatory coding, possibly leading to reduced appeal, [19] and prompts the release of satiety hormones (e.g., CCK [20]) to terminate ingestion. Further, CD36-null mice that are insensitive to fatty acids [21],
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have higher resting fatty acid and triacylglycerol (TAG) concentrations than wild type animals [22]. This review will summarize current knowledge about human fat perception and the effects of orosensory exposure to fat on lipid metabolism and feeding. 1. The basis for fat hedonics The orosensory properties of fats stimulate ingestion in rats. This occurs in deprived and sated sham-feeding animals for nutritive (vegetable oil) and non-nutritive (mineral oil) stimuli as well as in intact and ventromedial hypothalamus (VMH)lesioned animals [23,24]. When food deprived, rats express a preference for a mineral oil emulsion over a highly preferred, saccharin solution [25]. Thus, ingestion of fats occurs in the absence of feedback regarding energy status. However, even under such conditions, corn oil is preferred to mineral oil. While the exact nature of the stimulus properties allowing discrimination between corn and mineral oils is presently unknown, this rules out a number of features, such as viscosity, as the predominant sensory property promoting corn oil intake over intake of mineral oil. The question about whether humans have an innate liking for fat has not been resolved. Intra-amniotic injection of 3 – 8 ml of Lipiodol (iodinated poppy seed oil) reduces fetal drinking [26], whereas prior work had demonstrated that injection of sodium saccharin stimulates drinking [27]. The latter has been interpreted as evidence of fetal expression of a positive hedonic response (for sweet taste). The former could thus be interpreted as a negative response to fat, except that the iodine adds a flavor note that may be responsible for the rejection. A second approach to answer this question has been to monitor the sucking and ingestive behaviors of neonates exposed to formula or breast milk of varying fat content. This stems from the observation that the fat content of breast milk increases during suckling and could serve as a signal to terminate feeding. Given the common assumption that fat is palatable, this is an interesting concept since it would predict that an increasingly palatable stimulus would provide a stopping cue for feeding. Nevertheless, the results of such studies are indecisive. Provision of low fat and high fat breast milk samples for 2min intake trials revealed no difference in volume consumed [28]. A lack of effect was also reported in a trial of 5-month-old infants provided three formulas varying in fat [29]. Further, oral stimulation with fat failed to modify crying, mouthing or hand to mouth contact in newborns, whereas both sucrose and quinine were effective [30]. These observations could be due to a lack of ability to detect fat or, more likely, hedonic indifference. In contrast, stronger sucking responses have been reported for high-fat formula compared to a low-fat equivalent, indicating preference for fat [31]. In yet another approach, hedonic responses of children to novel and familiar foods characterized as predominantly sweet, salty, sour, bitter or fatty revealed that the high fat foods were most preferred [32]. Further, the discrepancy between responses to the novel and familiar foods were smallest for the high-fat items. That is, the high-fat foods elicited the weakest neophobic response.
Regardless of any inherent liking or disliking of fat, its hedonic valence may be overridden by dietary experience [33,34]. Under extreme conditions, fat is a very salient dietary cue for cue-consequence learning. High fat foods are common targets for food aversions in humans [35]. Animal [3] and human [36] studies show fat can also aid in learned preferences. With normal eating, the preferred concentration of fat in foods may be more closely related to the customary level of exposure to its sensory properties than the metabolic consequence of its ingestion [34]. This allows the flexibility to learn to like the available food supply and is consistent with the reluctance of humans to abandon the flavor principles of their culture [37]. 2. How is fat detected? Expression of fat preference requires first that it be detected. The mechanisms by which this occurs are rapidly being clarified. One observation is undoubtedly true, fats are perceived by multiple mechanisms. While visual and auditory cues aid in identification of the fat content of foods, most work has focused on textural, olfactory and taste properties. 3. Texture Evidence that dietary fats impart textural attributes to foods is compelling. In free-choice profiling, the terms consumers use to rank fat content are primarily textural [38]. Higher and lower fat milk samples are differentiated by terms such as, buttery/ fatty/greasy/oily, creamy/rich and thin/watery. This may be because terms for the olfactory and taste components of fats are not familiar to consumers. The ability to discriminate fat content is comparable when the samples are presented orally, with the nose pinched shut to block olfactory input, and when the samples are rubbed between two fingers, providing only textural input [39]. An initial assumption was that the relevant textural property was viscosity. However, electrophysiological recordings and behavioral data suggest viscosity may not be the only textural cue for fat. Lubricity may be another relevant tactile attribute [40,41]. Still, texture does not fully account for fat detection. When oils are heated, their texture changes, but perceived fat content does not [42] and at a constant viscosity perceived fat content differs with varying emulsion particle size and fat saturation [43]. Most recently, fMRI studies in humans have documented responses to fat independent of its viscosity [44]. Importantly, neural responsiveness to fats is modulated by their recent ingestion. When sated, responsiveness declines [45]. 4. Olfaction There is also an olfactory component to fat perception. Rats exhibit a preference for unsaturated fatty acid solutions in brief ingestion tests at concentrations in the range of 0.1– 1.0% w/w. When olfactory function is eliminated by sinus irrigation with zinc sulfate [46], or olfactory bulbectomy [47], the preference for weak fatty acid stimuli over vehicle is eliminated. A
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5. Taste Evidence supporting a taste component to fat perception is rapidly accumulating from varied sources. Cis-long-chain, polyunsaturated and monounsaturated fatty acids depolarize taste receptor cells of rats [52]. They do so in a reversible manner with a time course consistent with detection of fat in foods (reviewed by Gilbertson in this special issue). Further, the pharyngeal branch of the glossopharyngeal nerve is activated by linoleic and oleic acids, but not triolein, mineral oil, paraffin oil or vegetable oil [53]. Behavioral assays with mice and rats are consistent with a taste component. This work has largely entailed monitoring fluid intake during brief ingestion trials (to minimize postingestive cues) where potential textural cues are masked by the addition of a thickening agent such as xanthan gum. In such trials, 0.2– 1% concentrations of oleic, linoleic and linolenic acids are preferred over the vehicle or triolein [46,54]. Similar findings are reported for corn oil [55]. Further, linoleic acid solutions are preferred over oleic acid and linolenic acid is preferred over linoleic acid [54]. However, this work cannot be viewed as definitive as there was no control over olfactory cues, the possible presence of oxidation products [56,57] or other cues [58] that may have been the true effective stimulus. Taste aversion paradigms reveal rats detect corn oil [59] and likely use the same transduction mechanism for linoleic and oleic fatty acids [60]. Psychophysical data on human fat taste are limited. Findings reported in an abstract [61] indicate humans can detect deodorized TAG when placed on the posterior lateral tongue when tongue movement is controlled to minimize tactile cues. One small (n = 20) study designed to explore racial differences
in fat perception and preference in 9– 15 year olds used a matrix of fluid dairy products with graded concentrations of fat and sucrose [62]. Texture was masked by the addition of 0.5% sucrose stearate. Thresholds were 0.75 T 0.29%w/v (African American) and 2.28 T 0.9%w/v (White) and were not significantly different with and without nose clips. No significant racial differences were observed in discrimination or hedonics. A follow-up study with young adults using deodorized corn oil and butterfat emulsions yielded similar findings [62]. Young (n = 12) and elderly (n = 12) individuals have been tested with and without nose clips using oil in water emulsions of deodorized soybean oil, a long-chain triglyceride oil, medium-chain triglyceride oil and light mineral oil (non-nutritive). Four emulsifiers were tested. The young had lower detection thresholds (5.3% v/v) compared to the elderly (15.8% v/v). Odor cues did not improve performance. Acacia, which does not react chemically with the fat, was the emulsifier yielding the lowest thresholds. These values for triglycerides are higher than the typically reported thresholds of 0.5 –1% for fatty acids in electrophysiological and animal behavioral tests. This could be because the fatty acid is the effective stimulus and humans have no appreciable lingual lipase concentration to hydrolyze the triglyceride [63], but high-fat foods can have non-esterified fatty acid concentrations >0.5% [64,65]. We (RM and Angela Chale-Rush) have recently initiated a series of studies to measure thresholds for linoleic (polyunsaturated), oleic (monounsaturated) and stearic (saturated) fatty acids in humans. To minimize a potential contribution of fatty acid degradation products in detection tasks, stimuli contain EDTA, are prepared by sonication to minimize exposure to light and heat and are stored under nitrogen. To eliminate odor cues, testing is conducted with nares blocked. Textural cues are addressed by using both mineral oil and acacia gum in the vehicle to provide viscosity and lubricity. These safeguards, in conjunction with the preparation and storage of samples in polypropylene vessels to reduce fat adhesion to container walls, result in homogeneous samples. The concentrations and purity are verified by gas chromatography. Thresholds are determined by a three-alternative, forced-choice ascending staircase procedure to minimize fatigue and adaptation effects. Stimuli are presented to participants in a timed protocol with instructions to identify the sample containing the fat. Correct identification results in presentation of the same three stimuli, 5
Concentration (%w/v)
preference for stronger concentrations is diminished but present. Similar results have been reported with mice [48]. Electrophysiological recordings of Macaques demonstrate that the odor of fat is a sufficient stimulus for its detection in foods [45]. However, bilateral bulbar lesions covering much of the reported fatty acid responsive areas in rats do not result in loss of ability to discriminate between the odors of short chain fatty acids [49]. The applicability of this observation for perception of longer-chain fatty acids, which may use different transduction mechanisms, is uncertain. Evidence that olfaction contributes to fat discrimination in humans is mixed. In some work closing the nares fails to alter performance on detection tasks [39,50], whereas other work suggests thresholds are higher without the olfactory component (Gilbertson, personal communication). Studies using the change of plasma TAG as a biomarker of sensory detection of dietary fat fail to support an olfactory contribution [51]. However, it is not clear from this work whether the stimulus was not detected or it just failed to alter the TAG concentration following exposure. The variability in responses to olfactory stimulation may be related to the concentration of oxidation products in the test fats. The rancid odor of an oxidized fat is readily detectable and such products form rapidly upon exposure of fatty acids to air, light and elevated temperature.
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4 3 2 1 0 Linoleic Acid
Oleic Acid
Stearic Acid
Mineral Oil
Fig. 1. (Mean (S.E.) human (N = 5) fatty acid detection thresholds.
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and an incorrect identification is followed with the next higher sample concentration. Testing stops with three consecutive correct identifications ( p < 0.05). Preliminary findings are consistent with humans having the ability to detect 18C fatty acids of varying saturation (Fig. 1). 6. Individual variability in fat taste Part of the difficulty in determining whether there is a taste component to fat in humans may be due to marked individual variability. Fat sensitive and insensitive rats have been identified [66]. The Osborne – Mendel strain has a predominance of Kv2/Kv3 channels relative to Kv1 on their taste receptor cells. They are relatively insensitive to long-chain polyunsaturated fatty acids. In contrast, the S5B/P1strain has the reverse configuration and is more sensitive. Interestingly, the former are fat preferring and are obesity prone, whereas the latter avoid fat and are obesity resistant. Attempts to demonstrate a dichotomy for fat taste in humans have yielded mixed results. In one trial, individuals were provided 12 pairs of 10 AM solutions of linoleic acid or vehicle. If, after two practice trials, participants could correctly identify the sample containing the fatty acid in 9 or 10 of 10 pairs, they were classified as fatty acid tasters. Approximately 10 of 24 participants were so classified [67]. The reliability of the classification is reported as 95% when individuals are tested twice, 1 week apart. Interpretation of the classification test is problematic since it is not clear that detection is not based on odor or texture and the acids were sodium salts which are not present in foods. Nevertheless, individuals classified by this approach were not able to differentiate between ice cream samples prepared with known amounts of sodium salts of linoleic and oleic fatty acids. Both groups of participants generally reported supplemented samples were creamier, a textural attribute, but there were no group differences in hedonic ratings for the samples. In addition, there were no group differences in meal size, meal duration, eating rate or change of satiety [67]. There was an interaction wherein linoleic acid tasters exhibited a significant association between amount eaten of some samples and reported change of satiety. The meaning of this observation, which was not noted in the linoleic acid non-tasters, is uncertain. In other work, individual differences in fat taste have been linked with propylthiouracil (PROP) taste sensitivity. The association is based on the assumption that PROP tasters have a higher density of taste papillae with resulting richer trigeminal innervation and greater sensitivity to the texture of fats. There is a report that, unlike PROP non-tasters, tasters are able to distinguish between salad dressings containing 10% and 40% fat [68]. However, while the tasters could discriminate between the samples, they showed no differential hedonic response to them and the non-tasters, who did not detect differences, reported a preference for the 40% fat sample. Later work suggested non-taster, female, but not male, children rate selected high fat foods (e.g., milk, cheese) as more pleasant and have higher reported intake of discretionary fats [69]. A similar
gender difference has also been noted with young adults [70]. Others have not been able to reproduce these findings [71,72] and there is evidence to the contrary (i.e., PROP non-tasters consumed less fat in a preload study [73]). Taken together it is not clear that there is a dichotomy in human fat taste sensitivity. Studies using more tightly controlled stimuli will be needed to confirm or refute the hypothesis of such a classification and its nutritional implications. 7. Cephalic phase fat response Evidence is accumulating that orosensory detection of fat provides a signal leading to modulation of subsequent responsiveness to the substance. That is, there is a cephalic phase fat response. Early human work revealed that meal (not containing Vitamin A) ingestion after loading with lipid containing Vitamin A prompts a rapid rise in plasma Vitamin A concentration [74]. Modified sham feeding produced the same effect and it was blocked by administration of atropine. Because Vitamin A is lipophilic, this suggested that oral exposure to the meal elicited a neurally mediated augmentation of lipid (derived from the Vitamin A load) absorption from the GI tract. This human work was followed by animal studies demonstrating lipid absorption was preferentially augmented by oral exposure to dietary fat [75]. Subsequent studies in humans have confirmed and better characterized the phenomenon. Following ingestion of 50 g of safflower oil in capsules, to eliminate oral fat exposure, modified sham feeding with full-fat cream cheese prompts a larger postprandial increase of TAG than oral exposures to fat-free cream cheese, the cracker vehicle or no oral stimulation [76]. Because the full-fat and fatfree cream cheese stimuli were not distinguishable based on texture or appearance, the oral stimuli were not swallowed and participants were blinded to sample composition, it was hypothesized that a chemosensory detection system for dietary fat was involved. This was supported by evidence that protein, carbohydrate and fat-based fat replacers did not augment the postprandial TAG concentration, nor did the vehicle, whereas butter was effective [77]. Based on evidence available at the time, it was assumed the cue was olfactory. Another study provided participants oral (olfactory and taste), orthonasal or no olfactory stimulation to cream cheese with or without prior lipid loading. Oral exposure augmented the TAG rise relative to the other treatments. Because the olfactory stimulation alone was ineffective, it appeared the taste component from the oral exposure was the salient cue. This was supported by findings that adding a test with nares blocked (taste only) led to a TAG rise comparable to that noted with oral exposure [51]. Analyses of expectorated saliva revealed linoleic and oleic fatty acids in concentrations sufficient to elicit taste receptor cell depolarization, assuming humans are as sensitive to fatty acids as rats [52]. Additional studies indicated oral exposure to saturated fat was not as effective [78]. Further studies are needed to better characterize the fatty acid specificity of the effect, the level of exposure required to elicit it (i.e., does it have dietary relevance) and whether there are interactions between sensory
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properties of foods or nutrients that augment or diminish the response. With respect to the mode of action, oral stimulation could enhance lipid absorption, promote de novo lipogenesis or reduce lipid clearance. Most work to-date has focused on absorptive processes. In studies where successive meals contained different fatty acid profiles, the ingestion of the latter was shown to prompt mobilization of lipids derived from the former (second meal effect) [79]. Later work demonstrated lipid from the first meal was stored in jejunal enterocytes [80]. Modified sham feeding was tested to determine whether the lipid could be mobilized by orosensory stimulation alone. One attempt failed to support this phenomenon, but blood samples were collected infrequently during the critical early postexposure period [81]. With more rapid sampling, orosensory stimulation, particularly with a dietary fat source, resulted in an early (within 15 –30 min post-stimulation onset) TAG peak in 25 of 25 participants [82]. By again providing fatty acids of different saturation, at the successive eating occasions, it was demonstrated that this early peak was enriched in lipid from the first meal. Moreover, the magnitude of the first peak was significantly correlated with the subsequent peak occurring approximately 2 h after ingestion of the second meal. Stable isotope studies are now underway to confirm the origin and fate of TAG appearing in the plasma following orosensory stimulation with fat. Additional mechanisms may contribute to the orosensory modulation of lipid digestion and absorption in humans. A cephalic phase release of gastric lipase has been documented [83] that is ameliorated by atropine. While lipase activity is optimal in the acidic environment of the stomach, it retains substantial activity, ¨ 50%, at pH 6.5 so, can continue to hydrolyze TAG in the duodenum. An estimated 17% of TAG hydrolysis is attributable to gastric lipase [84]. GI transit is also modulated by orosensory stimulation. Oral intake results in slower gastric transit relative to infusion of the same load into the stomach. This was attributed to the sensory stimulation facilitating expression of feedback cues from further down the GI tract [85]. A cephalic phase release of CCK has also been reported [86]. Finally, studies in esphagotomized rats demonstrate that oral exposure to non-esterified linoleic, oleic and linolenic acids elicits secretion of digestive enzymes [87]. Consistent with the specificity of taste responses to fatty acids, methyl esters and a shorter chain fatty acid were not effective. Cephalic phase responses have also been identified that address other potential mechanisms for the orosensory stimulation of postprandial TAG. Modified sham-feeding of a high fat cake, but not a fat-free version, stimulates hepatic pancreatic polypeptide release [88]. This hormone stimulates VLDL synthesis and secretion. VLDL concentrations are elevated in humans after modified sham feeding conducted 1 h after ingestion of a lipid meal relative to no oral stimulation or stimulation provided 1 h before meal ingestion [89]. Given the greatest discrepancy in plasma TAG associated with oral stimulation occurs 4 –8 h after exposure, an effect on lipid clearance also seems likely. Sham feeding modulates lipoprotein lipase activity in adipocytes and myocytes [90]. Initially,
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activity is depressed in the former and augmented in the latter. There is no obvious primary route for sensory modulation of peripheral lipoprotein lipase. It may be a secondary response to orosensory stimulation of insulin secretion. Whether this contributes to a reduced TAG clearance is not known. 8. Summary Accumulating evidence suggests dietary fats are detected by textural, olfactory and taste mechanisms. The taste effects are subtle, likely vary with fatty acid saturation and chain length, could be altered by one’s energy balance and may be expressed differentially across individuals. With further verification of the transduction mechanisms and characterization of the effective stimuli, the question of whether ‘‘fatty’’ constitutes a basic taste may warrant consideration. The physiological and nutritional implications of fat sensing are broad. Oral fat exposure initiates cephalic phase responses throughout and beyond the GI tract. To date, documented effects include: gastric lipase secretion, modulated GI transit, pancreatic exocrine secretions, gut hormone release, mobilization of stored lipid from enterocytes, pancreatic endocrine secretion and altered lipoprotein lipase activity. Through the above activities, oral fat exposure may influence appetitive responses, food intake, nutritional status and disease risk. Intriguingly, differential responsiveness to fatty acids has been identified in obesity prone and resistant rats [66]. Attempts to identify differences in food choice or energy balance among humans varying in fat taste responsiveness are only beginning. Given the subtlety of the purported taste cue and multitude of factors that influence ingestive behavior, a primary causal relationship between fat taste and intake may be difficult to identify. However, with the broad distribution of common fatty acid sensors and stimuli in the body [6] taste may provide an index of systemic reactivity to fats which could exert a more profound influence on ingestive behavior. References [1] Putnam J, Allshouse J, Kantor LS. US per capita food supply trends: more calories, refined carbohydrates, and fats. FoodReview 2002;25:2 – 15. [2] Imaizumi M, Takeda M, Fushiki T. Effects of oil intake in the conditioned place preference test in mice. Brain Res 2000;870:150 – 6. [3] Elizalde G, Sclafani A. Fat appetite in rats: flavor preferences conditioned by nutritive and non-nutritive oil emulsions. Appetite 1990;15:189 – 97. [4] Kern DL, McPhee L, Fisher J, Johnson S, Birch LL. The postingestive consequences of fat condition preferences for flavors associated with high dietary fat. Physiol Behav 1993;54:71 – 6. [5] Ordway RW, Singer JJ, Walsh JV. Direct regulation of ion channels by fatty acids. TINS 1991;14:96 – 100. [6] Gilbertson TA, Kim I, Liu L. Sensory cues for dietary fat: implications for macronutrient preferences. In: Guy-Grand B, Ailhaud G, editors. 8th International Congress on Obesity. Progress in Obesity Research, vol. 8. 1999. p. 167 – 71. [7] Abumrad NA, Perkins RC, Park JH, Park CR. Mechanism of long-chain fatty acid permeation in the isolated adipocyte. J Biol Chem 1981;256: 9183 – 91. [8] Hauser H, Dyer JH, Nandy A, Vega MA, Werder M, Bieliauskaite E, et al. Identification of a receptor mediating absorption of dietary cholesterol in the intestine. Biochemistry 1998;37:17843 – 50.
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R.D. Mattes / Physiology & Behavior 86 (2005) 691 – 697 [59] Smith JC, Fisher EM, Malezewski V, McClain B. Orosensory factors in the ingestion of corn oil/sucrose mixtures by the rat. Physiol Behav 2000; 69:135 – 46. [60] Clyburn VL, Pittman DW. Gustatory detection of oleic acid and stimulus generalization to linoleic acid in rats. Association of Chemosensory Sciences 26th Annual Meeting, Sarasota, FL; 2004. [61] Schiffman SS, Graham BG, Vance AR, Gaillard K, Warwick ZS, Erickson RP. Detection thresholds for emulsified oils in young and elderly subjects. [Abstract]Chem Senses 1992;17:693. [62] Bacon AW, Miles JS, Schiffman SS. Effect of race on perception of fat alone and in combination with sugar. Physiol Behav 1994;55/3:603 – 6. [63] Spielman AI, D’Abundo S, Field RB, Schmale H. Protein analysis of human von Ebner saliva and a method for its collection from the foliate papillae. J Dent Res 1993;72:1331 – 5. [64] Weiss TJ. Food oils and their uses. Westport (CT)’ AVI Publishing; 1970. p. 22 – 3. [65] Smith LM, Cliford AJ, Hamblin CL, Creveling TK. Changes in physical and chemical properties of shortenings used for commercial deep fat frying. J Am Oil Chem Soc 1986;63:1017 – 23. [66] Gilbertson TA, Liu L, York DA, Bray GA. Dietary fat preferences are inversely correlated with peripheral gustatory fatty acid sensitivity. Reprinted from Olfaction and Taste XII, Annals of the New York Academy of Sciences, vol. 855; 1998 (Nov. 30). p. 165 – 8. [67] Kamphuis MMJW, Saris WHM, Westerterp-Plantenga MS. The effect of addition of linoleic acid on food intake regulation in linoleic acid tasters and linoleic acid non-tasters. Br J Nutr 2003;90:199 – 206. [68] Tepper BJ, Nurse RJ. Fat perception is related to PROP taster status. Physiol Behav 1997;61:949 – 54. [69] Keller KL, Steinmann L, Nurse RJ, Tepper BJ. Genetic taste sensitivity to 6-n propylthiouracil influences food preference and reported intake in preschool children. Appetite 2002;38:3 – 12. [70] Duffy VB, Bartoshuk LM. Food acceptance and genetic variation in taste. J Am Diet Assoc 2000;100:647 – 55. [71] Drewnowski A, Henderson SA, Barratt-Fornell A. Genetic sensitivity to 6-n-propylthiouracil and sensory responses to sugar and fat mixtures. Physiol Behav 1998;63:771 – 7. [72] Kamphuis MMJW, Westerterp-Plantenga MS, Saris WHM. Fat-specific satiety in humans for fat high in linoleic acid vs. fat high in oleic acid. Eur J Clin Nutr 2001;55:499 – 508. [73] Kamphuis MMJW, Westerterp-Plantenga MS. PROP sensitivity affects macronutrient selection. Physiol Behav 2003;79:167 – 72. [74] Mendeloff AI. The effects of eating and of sham feeding upon the absorption of vitamin A Palmitate in man. J Clin Invest 1954;33: 1015 – 21. [75] Ramirez I. Oral stimulation alters digestion of intragastric oil meals in rats. Am J Physiol 1985;248:R459 – 63.
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Fat taste and lipid metabolism in humans Richard D. Mattes * Purdue University, Department of Foods and Nutrition, 700 W State Street, W. Lafayette, IN 47907-2059, USA Received 12 July 2005; accepted 25 August 2005
Abstract Dietary and body fat are essential for life. Fatty acids modulate fat detection, ingestion, digestion, absorption and elimination. Though direct effects occur throughout the body, much of this regulation stems from signals originating in the oral cavity. The predominant orosensory cue for dietary fat is textural, but accumulating electrophysiological, behavioral and clinical evidence supports olfactory and gustatory components. Orosensory stimulation with long-chain unsaturated, but possibly also saturated, fatty acids elicits an array of cephalic phase responses including release of gastric lipase, secretion of pancreatic digestive enzymes, mobilization of lipid stored in the intestine from the prior meal, pancreatic endocrine secretion and, probably indirectly, altered lipoprotein lipase activity. Combined, these processes influence postprandial lipemia. There is preliminary evidence of marked individual variability in fat ‘‘taste’’ with uncertain health implications. The possibility that fat taste sensitivity reflects systemic reactivity to fat warrants further evaluation. D 2005 Elsevier Inc. All rights reserved. Keywords: Cephalic phase; Lipid; Fat; Taste; Smell; Texture; Chemosensory; Triacylglycerol; Fatty acid; Human
Despite two decades of fat vilification by the health care community and media, absolute intake of fat changed little and consumption remains high and is now growing [1]. A common argument for such a strong defense of fat intake is that the nutrient has provided some adaptive value. While associations with chronic diseases dominate current thought, the beneficial effects are diverse and multiple. Fats are: i) integral components of cell membranes, influencing their structure and function; ii) precursors for eicosinoids that regulate blood clotting, blood pressure and immune function as well as hormones critical for reproductive function (e.g., estrogens, testosterone) and bone health (calcitriol); iii) a carrier for fat soluble vitamins; iv) a thermal insulator; v) a shock absorber; vi) an energy substrate and vii) a source of sensory stimulation. Consequently, it is plausible that mechanisms evolved to promote fat intake. One potential mechanism is an orosensory capability to detect dietary fat coupled with a positive hedonic impression. This system may take several forms. First, the sensory impression could be inherently appealing. Second, orosensory detection initiates neurally mediated physiological
* Tel.: +1 765 494 0662; fax: +1 765 494 0674. E-mail address: [email protected]. 0031-9384/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.physbeh.2005.08.058
responses (cephalic phase responses) that reinforce ingestion [2]. Third, the metabolic feedback following actual ingestion of such an energy dense substance is rewarding [3,4]. Recently, evidence has emerged that fatty acids are ‘‘tasted’’ in post-oral regions of the GI tract and in the periphery with implications for ingestion. The term ‘‘taste’’ is used for sensing fatty acids outside the oral cavity because taste transduction mechanisms reportedly present in the oral cavity for fatty acids are ubiquitous. For example, delayed rectifying potassium channels linked to fat detection by oral taste receptor cells are also present in the intestine, pancreas, liver and heart [5,6]. The fatty acid transporter protein, CD36, is located on oral taste receptor cells as well as in the intestine, adipose tissue, skeletal muscle, heart and brain [7– 12]. Within the intestine, CD36 mediates the release of hormones linked to appetite such as CCK [13] and PYY [14]. While the biophysics of these transduction mechanisms is common, the effects vary markedly with site and may provide an integrated system for the control of fat intake and metabolism [15 –18]. For example, dietary lipid in the mouth may promote ingestion while its later presence in the intestine alters gustatory coding, possibly leading to reduced appeal, [19] and prompts the release of satiety hormones (e.g., CCK [20]) to terminate ingestion. Further, CD36-null mice that are insensitive to fatty acids [21],
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have higher resting fatty acid and triacylglycerol (TAG) concentrations than wild type animals [22]. This review will summarize current knowledge about human fat perception and the effects of orosensory exposure to fat on lipid metabolism and feeding. 1. The basis for fat hedonics The orosensory properties of fats stimulate ingestion in rats. This occurs in deprived and sated sham-feeding animals for nutritive (vegetable oil) and non-nutritive (mineral oil) stimuli as well as in intact and ventromedial hypothalamus (VMH)lesioned animals [23,24]. When food deprived, rats express a preference for a mineral oil emulsion over a highly preferred, saccharin solution [25]. Thus, ingestion of fats occurs in the absence of feedback regarding energy status. However, even under such conditions, corn oil is preferred to mineral oil. While the exact nature of the stimulus properties allowing discrimination between corn and mineral oils is presently unknown, this rules out a number of features, such as viscosity, as the predominant sensory property promoting corn oil intake over intake of mineral oil. The question about whether humans have an innate liking for fat has not been resolved. Intra-amniotic injection of 3 – 8 ml of Lipiodol (iodinated poppy seed oil) reduces fetal drinking [26], whereas prior work had demonstrated that injection of sodium saccharin stimulates drinking [27]. The latter has been interpreted as evidence of fetal expression of a positive hedonic response (for sweet taste). The former could thus be interpreted as a negative response to fat, except that the iodine adds a flavor note that may be responsible for the rejection. A second approach to answer this question has been to monitor the sucking and ingestive behaviors of neonates exposed to formula or breast milk of varying fat content. This stems from the observation that the fat content of breast milk increases during suckling and could serve as a signal to terminate feeding. Given the common assumption that fat is palatable, this is an interesting concept since it would predict that an increasingly palatable stimulus would provide a stopping cue for feeding. Nevertheless, the results of such studies are indecisive. Provision of low fat and high fat breast milk samples for 2min intake trials revealed no difference in volume consumed [28]. A lack of effect was also reported in a trial of 5-month-old infants provided three formulas varying in fat [29]. Further, oral stimulation with fat failed to modify crying, mouthing or hand to mouth contact in newborns, whereas both sucrose and quinine were effective [30]. These observations could be due to a lack of ability to detect fat or, more likely, hedonic indifference. In contrast, stronger sucking responses have been reported for high-fat formula compared to a low-fat equivalent, indicating preference for fat [31]. In yet another approach, hedonic responses of children to novel and familiar foods characterized as predominantly sweet, salty, sour, bitter or fatty revealed that the high fat foods were most preferred [32]. Further, the discrepancy between responses to the novel and familiar foods were smallest for the high-fat items. That is, the high-fat foods elicited the weakest neophobic response.
Regardless of any inherent liking or disliking of fat, its hedonic valence may be overridden by dietary experience [33,34]. Under extreme conditions, fat is a very salient dietary cue for cue-consequence learning. High fat foods are common targets for food aversions in humans [35]. Animal [3] and human [36] studies show fat can also aid in learned preferences. With normal eating, the preferred concentration of fat in foods may be more closely related to the customary level of exposure to its sensory properties than the metabolic consequence of its ingestion [34]. This allows the flexibility to learn to like the available food supply and is consistent with the reluctance of humans to abandon the flavor principles of their culture [37]. 2. How is fat detected? Expression of fat preference requires first that it be detected. The mechanisms by which this occurs are rapidly being clarified. One observation is undoubtedly true, fats are perceived by multiple mechanisms. While visual and auditory cues aid in identification of the fat content of foods, most work has focused on textural, olfactory and taste properties. 3. Texture Evidence that dietary fats impart textural attributes to foods is compelling. In free-choice profiling, the terms consumers use to rank fat content are primarily textural [38]. Higher and lower fat milk samples are differentiated by terms such as, buttery/ fatty/greasy/oily, creamy/rich and thin/watery. This may be because terms for the olfactory and taste components of fats are not familiar to consumers. The ability to discriminate fat content is comparable when the samples are presented orally, with the nose pinched shut to block olfactory input, and when the samples are rubbed between two fingers, providing only textural input [39]. An initial assumption was that the relevant textural property was viscosity. However, electrophysiological recordings and behavioral data suggest viscosity may not be the only textural cue for fat. Lubricity may be another relevant tactile attribute [40,41]. Still, texture does not fully account for fat detection. When oils are heated, their texture changes, but perceived fat content does not [42] and at a constant viscosity perceived fat content differs with varying emulsion particle size and fat saturation [43]. Most recently, fMRI studies in humans have documented responses to fat independent of its viscosity [44]. Importantly, neural responsiveness to fats is modulated by their recent ingestion. When sated, responsiveness declines [45]. 4. Olfaction There is also an olfactory component to fat perception. Rats exhibit a preference for unsaturated fatty acid solutions in brief ingestion tests at concentrations in the range of 0.1– 1.0% w/w. When olfactory function is eliminated by sinus irrigation with zinc sulfate [46], or olfactory bulbectomy [47], the preference for weak fatty acid stimuli over vehicle is eliminated. A
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5. Taste Evidence supporting a taste component to fat perception is rapidly accumulating from varied sources. Cis-long-chain, polyunsaturated and monounsaturated fatty acids depolarize taste receptor cells of rats [52]. They do so in a reversible manner with a time course consistent with detection of fat in foods (reviewed by Gilbertson in this special issue). Further, the pharyngeal branch of the glossopharyngeal nerve is activated by linoleic and oleic acids, but not triolein, mineral oil, paraffin oil or vegetable oil [53]. Behavioral assays with mice and rats are consistent with a taste component. This work has largely entailed monitoring fluid intake during brief ingestion trials (to minimize postingestive cues) where potential textural cues are masked by the addition of a thickening agent such as xanthan gum. In such trials, 0.2– 1% concentrations of oleic, linoleic and linolenic acids are preferred over the vehicle or triolein [46,54]. Similar findings are reported for corn oil [55]. Further, linoleic acid solutions are preferred over oleic acid and linolenic acid is preferred over linoleic acid [54]. However, this work cannot be viewed as definitive as there was no control over olfactory cues, the possible presence of oxidation products [56,57] or other cues [58] that may have been the true effective stimulus. Taste aversion paradigms reveal rats detect corn oil [59] and likely use the same transduction mechanism for linoleic and oleic fatty acids [60]. Psychophysical data on human fat taste are limited. Findings reported in an abstract [61] indicate humans can detect deodorized TAG when placed on the posterior lateral tongue when tongue movement is controlled to minimize tactile cues. One small (n = 20) study designed to explore racial differences
in fat perception and preference in 9– 15 year olds used a matrix of fluid dairy products with graded concentrations of fat and sucrose [62]. Texture was masked by the addition of 0.5% sucrose stearate. Thresholds were 0.75 T 0.29%w/v (African American) and 2.28 T 0.9%w/v (White) and were not significantly different with and without nose clips. No significant racial differences were observed in discrimination or hedonics. A follow-up study with young adults using deodorized corn oil and butterfat emulsions yielded similar findings [62]. Young (n = 12) and elderly (n = 12) individuals have been tested with and without nose clips using oil in water emulsions of deodorized soybean oil, a long-chain triglyceride oil, medium-chain triglyceride oil and light mineral oil (non-nutritive). Four emulsifiers were tested. The young had lower detection thresholds (5.3% v/v) compared to the elderly (15.8% v/v). Odor cues did not improve performance. Acacia, which does not react chemically with the fat, was the emulsifier yielding the lowest thresholds. These values for triglycerides are higher than the typically reported thresholds of 0.5 –1% for fatty acids in electrophysiological and animal behavioral tests. This could be because the fatty acid is the effective stimulus and humans have no appreciable lingual lipase concentration to hydrolyze the triglyceride [63], but high-fat foods can have non-esterified fatty acid concentrations >0.5% [64,65]. We (RM and Angela Chale-Rush) have recently initiated a series of studies to measure thresholds for linoleic (polyunsaturated), oleic (monounsaturated) and stearic (saturated) fatty acids in humans. To minimize a potential contribution of fatty acid degradation products in detection tasks, stimuli contain EDTA, are prepared by sonication to minimize exposure to light and heat and are stored under nitrogen. To eliminate odor cues, testing is conducted with nares blocked. Textural cues are addressed by using both mineral oil and acacia gum in the vehicle to provide viscosity and lubricity. These safeguards, in conjunction with the preparation and storage of samples in polypropylene vessels to reduce fat adhesion to container walls, result in homogeneous samples. The concentrations and purity are verified by gas chromatography. Thresholds are determined by a three-alternative, forced-choice ascending staircase procedure to minimize fatigue and adaptation effects. Stimuli are presented to participants in a timed protocol with instructions to identify the sample containing the fat. Correct identification results in presentation of the same three stimuli, 5
Concentration (%w/v)
preference for stronger concentrations is diminished but present. Similar results have been reported with mice [48]. Electrophysiological recordings of Macaques demonstrate that the odor of fat is a sufficient stimulus for its detection in foods [45]. However, bilateral bulbar lesions covering much of the reported fatty acid responsive areas in rats do not result in loss of ability to discriminate between the odors of short chain fatty acids [49]. The applicability of this observation for perception of longer-chain fatty acids, which may use different transduction mechanisms, is uncertain. Evidence that olfaction contributes to fat discrimination in humans is mixed. In some work closing the nares fails to alter performance on detection tasks [39,50], whereas other work suggests thresholds are higher without the olfactory component (Gilbertson, personal communication). Studies using the change of plasma TAG as a biomarker of sensory detection of dietary fat fail to support an olfactory contribution [51]. However, it is not clear from this work whether the stimulus was not detected or it just failed to alter the TAG concentration following exposure. The variability in responses to olfactory stimulation may be related to the concentration of oxidation products in the test fats. The rancid odor of an oxidized fat is readily detectable and such products form rapidly upon exposure of fatty acids to air, light and elevated temperature.
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4 3 2 1 0 Linoleic Acid
Oleic Acid
Stearic Acid
Mineral Oil
Fig. 1. (Mean (S.E.) human (N = 5) fatty acid detection thresholds.
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and an incorrect identification is followed with the next higher sample concentration. Testing stops with three consecutive correct identifications ( p < 0.05). Preliminary findings are consistent with humans having the ability to detect 18C fatty acids of varying saturation (Fig. 1). 6. Individual variability in fat taste Part of the difficulty in determining whether there is a taste component to fat in humans may be due to marked individual variability. Fat sensitive and insensitive rats have been identified [66]. The Osborne – Mendel strain has a predominance of Kv2/Kv3 channels relative to Kv1 on their taste receptor cells. They are relatively insensitive to long-chain polyunsaturated fatty acids. In contrast, the S5B/P1strain has the reverse configuration and is more sensitive. Interestingly, the former are fat preferring and are obesity prone, whereas the latter avoid fat and are obesity resistant. Attempts to demonstrate a dichotomy for fat taste in humans have yielded mixed results. In one trial, individuals were provided 12 pairs of 10 AM solutions of linoleic acid or vehicle. If, after two practice trials, participants could correctly identify the sample containing the fatty acid in 9 or 10 of 10 pairs, they were classified as fatty acid tasters. Approximately 10 of 24 participants were so classified [67]. The reliability of the classification is reported as 95% when individuals are tested twice, 1 week apart. Interpretation of the classification test is problematic since it is not clear that detection is not based on odor or texture and the acids were sodium salts which are not present in foods. Nevertheless, individuals classified by this approach were not able to differentiate between ice cream samples prepared with known amounts of sodium salts of linoleic and oleic fatty acids. Both groups of participants generally reported supplemented samples were creamier, a textural attribute, but there were no group differences in hedonic ratings for the samples. In addition, there were no group differences in meal size, meal duration, eating rate or change of satiety [67]. There was an interaction wherein linoleic acid tasters exhibited a significant association between amount eaten of some samples and reported change of satiety. The meaning of this observation, which was not noted in the linoleic acid non-tasters, is uncertain. In other work, individual differences in fat taste have been linked with propylthiouracil (PROP) taste sensitivity. The association is based on the assumption that PROP tasters have a higher density of taste papillae with resulting richer trigeminal innervation and greater sensitivity to the texture of fats. There is a report that, unlike PROP non-tasters, tasters are able to distinguish between salad dressings containing 10% and 40% fat [68]. However, while the tasters could discriminate between the samples, they showed no differential hedonic response to them and the non-tasters, who did not detect differences, reported a preference for the 40% fat sample. Later work suggested non-taster, female, but not male, children rate selected high fat foods (e.g., milk, cheese) as more pleasant and have higher reported intake of discretionary fats [69]. A similar
gender difference has also been noted with young adults [70]. Others have not been able to reproduce these findings [71,72] and there is evidence to the contrary (i.e., PROP non-tasters consumed less fat in a preload study [73]). Taken together it is not clear that there is a dichotomy in human fat taste sensitivity. Studies using more tightly controlled stimuli will be needed to confirm or refute the hypothesis of such a classification and its nutritional implications. 7. Cephalic phase fat response Evidence is accumulating that orosensory detection of fat provides a signal leading to modulation of subsequent responsiveness to the substance. That is, there is a cephalic phase fat response. Early human work revealed that meal (not containing Vitamin A) ingestion after loading with lipid containing Vitamin A prompts a rapid rise in plasma Vitamin A concentration [74]. Modified sham feeding produced the same effect and it was blocked by administration of atropine. Because Vitamin A is lipophilic, this suggested that oral exposure to the meal elicited a neurally mediated augmentation of lipid (derived from the Vitamin A load) absorption from the GI tract. This human work was followed by animal studies demonstrating lipid absorption was preferentially augmented by oral exposure to dietary fat [75]. Subsequent studies in humans have confirmed and better characterized the phenomenon. Following ingestion of 50 g of safflower oil in capsules, to eliminate oral fat exposure, modified sham feeding with full-fat cream cheese prompts a larger postprandial increase of TAG than oral exposures to fat-free cream cheese, the cracker vehicle or no oral stimulation [76]. Because the full-fat and fatfree cream cheese stimuli were not distinguishable based on texture or appearance, the oral stimuli were not swallowed and participants were blinded to sample composition, it was hypothesized that a chemosensory detection system for dietary fat was involved. This was supported by evidence that protein, carbohydrate and fat-based fat replacers did not augment the postprandial TAG concentration, nor did the vehicle, whereas butter was effective [77]. Based on evidence available at the time, it was assumed the cue was olfactory. Another study provided participants oral (olfactory and taste), orthonasal or no olfactory stimulation to cream cheese with or without prior lipid loading. Oral exposure augmented the TAG rise relative to the other treatments. Because the olfactory stimulation alone was ineffective, it appeared the taste component from the oral exposure was the salient cue. This was supported by findings that adding a test with nares blocked (taste only) led to a TAG rise comparable to that noted with oral exposure [51]. Analyses of expectorated saliva revealed linoleic and oleic fatty acids in concentrations sufficient to elicit taste receptor cell depolarization, assuming humans are as sensitive to fatty acids as rats [52]. Additional studies indicated oral exposure to saturated fat was not as effective [78]. Further studies are needed to better characterize the fatty acid specificity of the effect, the level of exposure required to elicit it (i.e., does it have dietary relevance) and whether there are interactions between sensory
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properties of foods or nutrients that augment or diminish the response. With respect to the mode of action, oral stimulation could enhance lipid absorption, promote de novo lipogenesis or reduce lipid clearance. Most work to-date has focused on absorptive processes. In studies where successive meals contained different fatty acid profiles, the ingestion of the latter was shown to prompt mobilization of lipids derived from the former (second meal effect) [79]. Later work demonstrated lipid from the first meal was stored in jejunal enterocytes [80]. Modified sham feeding was tested to determine whether the lipid could be mobilized by orosensory stimulation alone. One attempt failed to support this phenomenon, but blood samples were collected infrequently during the critical early postexposure period [81]. With more rapid sampling, orosensory stimulation, particularly with a dietary fat source, resulted in an early (within 15 –30 min post-stimulation onset) TAG peak in 25 of 25 participants [82]. By again providing fatty acids of different saturation, at the successive eating occasions, it was demonstrated that this early peak was enriched in lipid from the first meal. Moreover, the magnitude of the first peak was significantly correlated with the subsequent peak occurring approximately 2 h after ingestion of the second meal. Stable isotope studies are now underway to confirm the origin and fate of TAG appearing in the plasma following orosensory stimulation with fat. Additional mechanisms may contribute to the orosensory modulation of lipid digestion and absorption in humans. A cephalic phase release of gastric lipase has been documented [83] that is ameliorated by atropine. While lipase activity is optimal in the acidic environment of the stomach, it retains substantial activity, ¨ 50%, at pH 6.5 so, can continue to hydrolyze TAG in the duodenum. An estimated 17% of TAG hydrolysis is attributable to gastric lipase [84]. GI transit is also modulated by orosensory stimulation. Oral intake results in slower gastric transit relative to infusion of the same load into the stomach. This was attributed to the sensory stimulation facilitating expression of feedback cues from further down the GI tract [85]. A cephalic phase release of CCK has also been reported [86]. Finally, studies in esphagotomized rats demonstrate that oral exposure to non-esterified linoleic, oleic and linolenic acids elicits secretion of digestive enzymes [87]. Consistent with the specificity of taste responses to fatty acids, methyl esters and a shorter chain fatty acid were not effective. Cephalic phase responses have also been identified that address other potential mechanisms for the orosensory stimulation of postprandial TAG. Modified sham-feeding of a high fat cake, but not a fat-free version, stimulates hepatic pancreatic polypeptide release [88]. This hormone stimulates VLDL synthesis and secretion. VLDL concentrations are elevated in humans after modified sham feeding conducted 1 h after ingestion of a lipid meal relative to no oral stimulation or stimulation provided 1 h before meal ingestion [89]. Given the greatest discrepancy in plasma TAG associated with oral stimulation occurs 4 –8 h after exposure, an effect on lipid clearance also seems likely. Sham feeding modulates lipoprotein lipase activity in adipocytes and myocytes [90]. Initially,
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activity is depressed in the former and augmented in the latter. There is no obvious primary route for sensory modulation of peripheral lipoprotein lipase. It may be a secondary response to orosensory stimulation of insulin secretion. Whether this contributes to a reduced TAG clearance is not known. 8. Summary Accumulating evidence suggests dietary fats are detected by textural, olfactory and taste mechanisms. The taste effects are subtle, likely vary with fatty acid saturation and chain length, could be altered by one’s energy balance and may be expressed differentially across individuals. With further verification of the transduction mechanisms and characterization of the effective stimuli, the question of whether ‘‘fatty’’ constitutes a basic taste may warrant consideration. The physiological and nutritional implications of fat sensing are broad. Oral fat exposure initiates cephalic phase responses throughout and beyond the GI tract. To date, documented effects include: gastric lipase secretion, modulated GI transit, pancreatic exocrine secretions, gut hormone release, mobilization of stored lipid from enterocytes, pancreatic endocrine secretion and altered lipoprotein lipase activity. Through the above activities, oral fat exposure may influence appetitive responses, food intake, nutritional status and disease risk. Intriguingly, differential responsiveness to fatty acids has been identified in obesity prone and resistant rats [66]. Attempts to identify differences in food choice or energy balance among humans varying in fat taste responsiveness are only beginning. Given the subtlety of the purported taste cue and multitude of factors that influence ingestive behavior, a primary causal relationship between fat taste and intake may be difficult to identify. However, with the broad distribution of common fatty acid sensors and stimuli in the body [6] taste may provide an index of systemic reactivity to fats which could exert a more profound influence on ingestive behavior. References [1] Putnam J, Allshouse J, Kantor LS. US per capita food supply trends: more calories, refined carbohydrates, and fats. FoodReview 2002;25:2 – 15. [2] Imaizumi M, Takeda M, Fushiki T. Effects of oil intake in the conditioned place preference test in mice. Brain Res 2000;870:150 – 6. [3] Elizalde G, Sclafani A. Fat appetite in rats: flavor preferences conditioned by nutritive and non-nutritive oil emulsions. Appetite 1990;15:189 – 97. [4] Kern DL, McPhee L, Fisher J, Johnson S, Birch LL. The postingestive consequences of fat condition preferences for flavors associated with high dietary fat. Physiol Behav 1993;54:71 – 6. [5] Ordway RW, Singer JJ, Walsh JV. Direct regulation of ion channels by fatty acids. TINS 1991;14:96 – 100. [6] Gilbertson TA, Kim I, Liu L. Sensory cues for dietary fat: implications for macronutrient preferences. In: Guy-Grand B, Ailhaud G, editors. 8th International Congress on Obesity. Progress in Obesity Research, vol. 8. 1999. p. 167 – 71. [7] Abumrad NA, Perkins RC, Park JH, Park CR. Mechanism of long-chain fatty acid permeation in the isolated adipocyte. J Biol Chem 1981;256: 9183 – 91. [8] Hauser H, Dyer JH, Nandy A, Vega MA, Werder M, Bieliauskaite E, et al. Identification of a receptor mediating absorption of dietary cholesterol in the intestine. Biochemistry 1998;37:17843 – 50.
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