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Dietary fat content affects energy intake and weight gain independent of diet caloric density in rats
Physiology & Behavior 77 (2002) 85 – 90
Dietary fat content affects energy intake and weight gain independent of diet caloric density in rats Zoe S. Warwick*, Steven J. Synowski, Kimberly R. Bell Department of Psychology, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA Received 6 November 2001; received in revised form 30 April 2002; accepted 28 May 2002
Abstract Recent considerations of high-fat diet hyperphagia have focused on fat’s relatively high energy density as the critical variable which promotes overeating. However, a high-fat (HF) diet has been shown to enhance intake and weight gain relative to a high-carbohydrate (HC) diet when both energy density and palatability are equated [Am. J. Physiol. 269 (1995) R30]. The present studies investigated the generality of this finding across manipulations of diet caloric density, diet physical form, and chow availability. Separate groups of male rats were fed HF or HC at either 2.3 or 1.15 kcal/ml for 16 days; HF feeding enhanced weight gain relative to HC across both levels of energy density. HF hyperphagia also occurred when diets were presented in semisolid (gelled) form, and when chow was available in addition to liquid diet. These findings are consistent with previous observations that an HF diet can enhance daily kilocalorie intake and weight gain at least partly via a mechanism that is unrelated to caloric density. D 2002 Elsevier Science Inc. All rights reserved. Keywords: Dietary fat; Dietary carbohydrate; Caloric density; Hyperphagia
1. Introduction Consumption of a diet high in fat is often associated with greater caloric intake and weight gain than occurs on a lowfat diet. This has been revealed in epidemiological studies, via experimental manipulation of dietary fat content using human subjects, and in animal models of dietary-induced overeating (see Refs. [25,27] for reviews). However, dietary fat content has often been confounded with diet caloric density and/or palatability, making it difficult to interpret the findings in terms of a nutrient-specific effect of fat. High-fat (HF) foods have a reputation for being highly palatable, much more so than high-carbohydrate (HC) foods, and this is often taken to explain why HF diets promote hyperphagia. In humans, food fat content has been positively correlated with palatability ratings in aggregate [9], although there are marked inter- and intra-individual differences in hedonic response to increased dietary fat [15]. A role for palatability-induced enhancement of daily intake has been demonstrated in rats [20]; however, only a HC diet * Corresponding author. Tel.: +1-410-455-2360; fax: +1-410-4551055. E-mail address: [email protected] (Z.S. Warwick).
was used in this study and thus the findings do not illuminate the relative importance of palatability in determining intake of HF vs. HC diets. Evidence indicates, however, that a palatability advantage cannot completely account for HF diet-induced overeating. In one study [10], women ate diets containing either a low (15 – 20%), medium (30 –35%) or high (45 –50%) proportion of calories from fat for 2 weeks. Average daily calorie intake was positively related to dietary fat content, even though the HF diet tended to be rated as less palatable than the low-fat diet. Another study in which fat content was not systematically related to palatability also demonstrated increased caloric intake in response to increases in dietary fat content [21]. However, differences in fat content were confounded with differences in energy density, presenting an interpretive problem. Relative caloric density has been implicated in the excessive caloric intake associated with HF diets. A review [16] of human ingestive responses to manipulation of dietary fat indicates the tendency of subjects to eat a constant weight of food regardless of fat content (and caloric density), implicating mass and/or volume-related cues, such as stomach fill and/or number of bites, in the control of intake. Since fat is more calorically dense than either protein
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or carbohydrate, caloric intake and relative body weight should increase as dietary fat content and caloric density increase, as has been observed in free-living humans [11]. Epidemiological data are, however, difficult to interpret due to the covariance of dietary fat content with other dietary and lifestyle factors which affect energy balance. Controlled feeding studies demonstrate that simultaneous increases in dietary fat content and caloric density do enhance energy intake [6,10,21]. Additional evidence for the role for diet caloric density in intake regulation comes from studies in which dietary fat content was manipulated while keeping the caloric density of the diet constant; calorie intake did not differ across the various levels of fat [17,19,22,23]. The independent effects of dietary fat and energy density have been assessed directly in a series of experiments by Rolls et al. [1,2,17], who measured the effect of manipulating the fat content and energy density of foods on intake by women. Importantly, the palatability of all foods was similar. Subjects consumed fewer calories when the foods had lower energy density; fat content did not affect intake. A review of 40 animal studies [27] comparing energy regulation on HF vs. low-fat diets indirectly revealed the role of diet caloric density in hyperphagia. Of the studies in which the caloric density of the diets was similar (density of HF no more than 25% greater than HC, accomplished by dilution of the HF diet with inert material), greater weight gain by HF-fed rats relative to HC-fed rats was observed in only 5 out of the 10 studies. In contrast, when the caloric density of the HF diet markedly exceeded that of the HC diet (density of HF at least 25% greater than HC), 28 out of 30 studies observed greater weight gain by the HF-fed rats. However, because all diets were consumed orally, interpreting the results is problematic. The more calorically dense HF diets may have promoted greater weight gain because they were more palatable, produced less stomach distention per kilocalorie, and/or less potently stimulated pre- or postabsorbtive satiety signals. Together, these findings implicate HF foods’ caloric density, and potentially their palatability, as relevant attributes which promote overeating. However, the lack of HF diet overeating observed in studies in which energy density and palatability were controlled [2,19,22,23] does not imply that the nutrient-specific effects of fat play no role in promoting hyperphagia. Indeed, the hyperphagic effect of dietary fat, independent of energy density and palatability, has been demonstrated in animal studies. In a self-regulated intragastric feeding paradigm, rats infused either HF or HC liquid diets having identical energy density over 16 days. Since the diets were not tasted, the greater intake by rats infusing the HF diet directly demonstrated that the unique postingestive effects of fat can promote hyperphagia [30]. Subsequently, Lucas et al. [12] replicated this finding using a within-subjects paradigm. Studies focusing on short-term controls of feeding (meal size and postprandial satiety) have also demonstrated that increasing food fat content is often associated with larger meal size (reduced satiation) and with
greater subsequent intake (reduced postprandial satiety) (reviewed in Ref. [25]). The purpose of the present studies was to further investigate the hyperphagia induced by an HF diet that is isocaloric with an HC diet. Specifically, the generality of the phenomenon across manipulations of diet caloric density, diet physical form, and chow availability was examined. In Experiment 1, diet composition and caloric density were independently manipulated. Experiment 2 assessed the effect of changing the physical characteristics of the diets to a semisolid gel, as evidence suggests that the physical form of diets can affect intake [13]. Experiment 3 addressed the question of whether HF diet hyperphagia would persist even when a low-fat, nutritionally complete food (chow) was also available ad lib.
2. General methods 2.1. Animals and housing Male Long – Evans rats were individually housed in hanging wire mesh cages, with ad lib powdered chow (Purina 5001 Rodent chow, 3.3 kcal/g: 28% kcal from protein, 60% kcal from carbohydrate, 12% kcal from fat) and water except as noted. A 12:12 light/dark cycle was maintained. 2.2. Diets Liquid HF and HC diets, isocaloric at 2.3 kcal/ml, were prepared as described previously [30] using tap water, with the addition of micronutrients, which were dissolved in a small quantity of water prior to being added to the milk. (To permit their use in intragastric infusion paradigms as well as oral feeding studies [26,30], the protein content of these diets must be low, but in all other respects they are nutritionally complete.) Ingredients and macronutrient composition are listed in Table 1. Diluted versions of these diets were obtained by mixing appropriate volumes of diet and Table 1 Diet composition
Evaporated milk (ml) Sucrose (g) 44.4% corn oil emulsion (ml) Vitamin mixa (g) Mineral mixb (g) Water kcal/ml % kcal from fat % kcal from carbohydrate % kcal from protein a b
High-fat
High-carbohydrate
540 140 250 5.98 8.13 to bring volume to 1 l 2.3 60 33 7
540 390 – 5.98 8.13 to bring volume to 1 l 2.3 17 76 7
Lieber – Dicarli liquid diet vitamin mix (Dyets). Modified AIN-93G mineral mix (Dyets).
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tap water. Diets were presented in plastic bottles with rubber stoppers and stainless steel ball spouts. 2.3. Experiment 1: caloric density manipulation The purpose of this study was to determine whether diet caloric density affected the magnitude of overeating and weight gain associated with the HF liquid diet. 2.3.1. Method Forty rats (age 73 days) were divided into four weightmatched groups (mean body weight 315 g). Each group received one of the following diets as the sole source of nutrition for 16 days: HF at 2.3 kcal/ml, HF at 1.15 kcal/ml, HC at 2.3 kcal/ml, HC at 1.15 kcal/ml. Intakes were measured daily by weighing the food bottles to the nearest gram, and animals were weighed periodically. 2.3.2. Results Rats consuming the HF diet at 2.3 kcal/ml had greater daily intake (mean 120.6, S.E. 9.02 kcal) than rats consuming HC at 2.3 kcal/ml (mean 97.2, S.E. 6.08 kcal), t(18) = 2.15, P < .05. Due to leakage problems, reliable intake measurements could not be obtained for the diluted (1.15 kcal/ml) diets. The HF diets promoted greater body weight gain than the HC diets, independent of diet caloric density (Fig. 1). Statistically, this was reflected by a main effect of diet [ F(1,38) = 5.05]. Neither the main effect of density nor the Diet Density interaction was significant. 2.3.3. Discussion The HF diet promoted greater caloric intake and weight gain than the HC diet, consistent with previous findings [30]. Although kilocalorie intake of the diluted diets could not be measured, the similarity of weight gain within each diet type, irrespective of diet density (Fig. 1), suggests that rats fed the diluted diets consumed approximately the same
Fig. 1. Experiment 1. Body weight gain across 16 days for rats fed HF or HC at either 2.3 or 1.15 kcal/ml. Values are means ± S.E.M.
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daily kilocalorie as their counterparts fed the full-strength diets. To further explore the role of diet caloric density in intake and weight gain, 14 additional animals were divided into two weight-matched groups (mean body weight 360 g) and fed either HF or HC at an even lower density (0.575 kcal/ml) for 16 days. Food intake could not be measured reliably due to leakage problems. It is important to note that these rats had a higher starting body weight than animals consuming the more calorically dense diets and thus actual weight gains cannot be directly compared to the 2.3- and 1.15-kcal/ml groups. However, the macronutrient effect was again observed: rats fed HF gained more weight (mean 42.3, S.E. 3.97 g) than rats fed HC (mean 28.0, S.E. 4.40 g), t(12) = 2.41, P < .05. 2.4. Experiment 2: semisolid HF and HC diets Experiment 1 and previous findings [30] demonstrate that the liquid HF diet reliably increases caloric intake and weight gain relative to the liquid HC diet, and this effect persists even when diet energy density is decreased. HF and HC were originally developed in liquid form to permit the use of sham and intragastric feeding techniques to isolate orosensory and postingestive controls of feeding, respectively [30]. However, calories are not customarily ingested entirely in liquid form, and so it is important to ascertain whether HF hyperphagia generalizes beyond the liquid format. There is evidence that the physical form of the diet can affect intake: rats ate less of a fat option when presented in gel form relative to liquid emulsion [13]. The goals of Experiment 2 were twofold: to investigate whether HF elicited hyperphagia relative to HC when the diets were presented in semisolid form, and to obtain accurate measurements of intake of the diluted diets. 2.4.1. Method Seventeen rats (age 112 days) were divided into two weight-matched groups (mean body weight 438 g). Each group received either semisolid (gelled) HF or HC (both at 1.15 kcal/ml) as the sole source of nutrition for 16 days. The gelled diets were prepared in the same manner as the liquid diets, with the following modifications. The water used to dissolve micronutrients was first heated to 80 °C. After the micronutrients had dissolved, 10 g of gelatin (Dyets, Bethlehem, PA) per liter of finished diet was added. When this had dissolved (approximately 5 min), diet preparation proceeded as described above. The finished diets were poured into stainless steel food cups and refrigerated for at least 3 h. Intakes were measured daily and animals were weighed periodically. 2.4.2. Results Rats fed the semisolid HF diet had greater intake (mean 119.0, S.E. 4.18 kcal/day) than rats fed the semisolid HC diet (mean 104.9, S.E. 4.35 kcal/day), t(15) = 2.89, P < .05
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(Fig. 2). Weight gain paralleled the difference in intake, with HF-fed rats gaining more weight than rats fed HC, t(15) = 2.35, P < .05 (Fig. 3). 2.4.3. Discussion When presented in semisolid (gelled) form, the HF diet promoted greater kilocalorie intake and weight gain than the HC diet, consistent with results obtained when these diets were liquids (Experiment 1; Ref. [30]). Because animals consuming the gel diets were not equivalent in terms of body weight to rats consuming the liquid diets, absolute weight gains cannot be compared across the two diet forms. Growth on the gel version of the 1.15-kcal/ml diets (Fig. 2) was more rapid than on the liquid versions (Fig. 1), possibly due to the different starting weights or to the greater protein fraction in the gel diets. Gelatin improved the protein fraction of the diets by about 50% (from 7% kcal in liquid diets to 10% kcal in gel diets). Daily intake of the gel diets may also have been slightly higher than their liquid counterparts since the gel was apparently more palatable; subsequent overnight two-choice tests with different animals (n = 8 per diet) revealed a clear preference for the gelled version over the liquid (HF mean intake of gel = 106.8 g, of liquid = 22.4 g; HC mean intake of gel = 64.3 g, of liquid = 26.0 g). 2.5. Experiment 3: liquid diets plus chow Experiments 1 and 2 verified the hyperphagia-promoting effect of the HF diet. However, in these studies, the liquid/ gelled diets were the sole nutrient source, which does not accurately model realistic eating in which a variety of both HF and low-fat foods are available. It is possible that the availability of a nutritionally complete low-fat food might attenuate the hyperphagia observed when HF is the sole source of nutrition. Therefore, a study was conducted in
Fig. 2. Experiment 2. Daily caloric intake averaged over 4-day blocks for rats fed gelled HF or HC. Values are means ± S.E.M.
Fig. 3. Experiment 2. Body weight gain across 16 days for rats fed gelled HF or HC. Values are means ± S.E.M.
which rats received ad lib powdered chow in addition to liquid diet. 2.5.1. Method Nineteen rats (age 53 days) were divided into two weight-matched groups (mean body weight 247 g). Each group received either HF or HC ad lib (both at 2.3 kcal/ml), in addition to ad lib chow. Intakes of chow and of liquid diet were measured daily and animals were weighed periodically. 2.5.2. Results Rats given HF consumed more liquid diet (mean 113.7, S.E. 5.05 kcal) than rats given HC (mean 70.0, S.E. 5.71 kcal), t(17) = 5.75, P < .001. Chow intake of HF-fed rats (mean 40.6, S.E. 3.42 kcal) was slightly lower than HC-fed rats (mean 49.9, S.E. 8.0 kcal), although this difference was not statistically significant. Thus, total daily kilocalorie intake (liquid diet + chow) was greater for rats fed HF (154.3, S.E. 6.69 kcal) than for rats fed HC (119.9, S.E. 3.95 kcal), t(17) = 4.30, P < .001 (Fig. 4).
Fig. 4. Experiment 3. Daily caloric intake averaged over 4-day blocks for rats fed chow and either HF or HC. Values are means ± S.E.M.
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Fig. 5. Experiment 3. Body weight gain across 16 days for rats fed chow and either HF or HC. Values are means ± S.E.M.
Body weight gain was rapid in all rats and was greater in HF-fed rats (avg 161.9, S.E. 15.3 g) than in HC-fed rats (avg 136.7, S.E. 12.5 g), although the difference did not reach statistical significance (Fig. 5). 2.5.3. Discussion The greater total kilocalorie intake (chow + liquid diet) by rats given HF vs. isoenergetic HC further illustrates that consuming a food high in fat increases total daily intake even when it is accompanied by a nutritionally complete, familiar food (chow) available ad libitum. These findings are consistent with another study which examined shortterm (22 h) energy intake in rats who self-infused either HF or HC while consuming chow ad libitum. Infusion of HF exceeded HC while chow intakes did not differ: thus total kilocalorie intake was greater on the HF infusion days [12].
3. General discussion A diet high in fat enhances daily caloric intake relative to a low-fat diet at least partly via a mechanism that is independent of caloric density. When HF and HC liquid diets were formulated to have equivalent caloric density, HF elicited greater intake when diets were consumed orally either with (Expt. 3) or without [30] ad lib chow; when diets were intragastrically infused either with [12] or without [30] ad lib chow; and when diets were gelled to semisolid form (Expt. 2). Dietary dilution did not negate the impact of high dietary fat; weight gain of HF-fed rats exceeded that of HCfed rats across three levels of diet caloric density (Expt. 1). These findings are consistent with analyses of acute (short-term) ingestive behavior in rat, which have demonstrated that meal size in terms of kilocalories is greater when HF is consumed relative to isoenergetic HC [26,29]. A preload of HF was less suppressive of subsequent intake (less satiating) than an isocaloric preload of HC, as indicated by relatively larger test meal intake following HF [26].
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Direct evidence that dietary fat can be less satiating than carbohydrate when chronically consumed in addition to chow comes from a study in which fixed quantities of either fat or carbohydrate were consumed, and spontaneous intake of chow measured. Rats consuming 30 ml/day of liquid diet in addition to chow ate more chow and thus more total kilocalories when given HF compared to HC [24]. Burggraf et al. [3] observed that intragastric infusion of fat, approximating 36% of baseline kilocalorie intake, suppressed oral intake less than isocaloric infusion of glucose. However, human preloading studies have yielded inconsistent findings regarding the relative satiety produced by fat vs. carbohydrate (reviewed in Refs. [18,25]). While some studies have found fat to produce less postprandial satiety than carbohydrate, in other instances, test meal intake following HF and HC preloads was similar (e.g. Refs. [5,8,28]). The test meals used in the latter studies may not have had appropriate sensitivity to detect macronutrient effects. A multi-item test lunch of familiar foods [28] elicited relatively high intake (approximately 1480 kcal), as did sweet, presumably novel liquid test meals (approximately 861 and 1177 ml in Refs. [5,8]), thus raising the possibility of a ceiling effect on intake. Since no-preload conditions were not run, this cannot be verified (although slight compensation for caloric vs. noncaloric preloads was observed in Ref. [8]). Human responsivity to macronutrients is complex and reflects the combined influence of sensory, postingestive, cognitive, and situational/methodological influences [4,18]. When liquid diets were available as an option in addition to chow, HF promoted greater total intake (chow + diet) than isoenergetic HC (Expt. 3; Ref. [12]). Previous observations of hyperphagia elicited by HF options relative to HC options have not dissociated macronutrient and caloric density effects [14]. Two pieces of evidence indicate that the greater intake of HF cannot be attributed to a palatability advantage. Intakes of HF and HC are similar in one-bottle sham-feeding tests [30], and more HF than HC is infused in a self-infusion paradigm in which diets are not tasted [12,30]. The mechanism(s) by which dietary fat promotes greater caloric intake is unknown but may relate to differences between the actions of fat and carbohydrate both pre- and postabsorbtively. Intragastric infusion of nutrient more effectively suppressed spontaneous food intake than an intravenous infusion; under both conditions, fat infusion was less suppressive than carbohydrate [3]. The relative proximity of the liver to the entry of energy substrates into the bloodstream may also be relevant, as the liver is implicated as a source of satiety signals [7]. Fat is absorbed into the lacteals and thus bypasses the liver while carbohydrates are absorbed into the portal vein. Daily kilocalorie intakes in Experiments 1 and 2 for rats HF-fed were approximately 120 kcal, and for rats fed HC were approximately 101 kcal, yet absolute weight gains in each diet group were greater in Experiment 2. This difference in weight gain was probably attributable to the increased
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protein content of the gel diets (Experiment 2) relative to the liquid diets (Experiment 1). Similarly, consumption of highprotein chow in addition to liquid diet (Experiment 3) no doubt facilitated growth. HF diets can promote weight gain that is disproportionally high relative to the increased caloric intake; indeed, weight gain on an HF diet can exceed that on an HC diet despite equivalent caloric intake [27]. The important observation is that across three feeding paradigms (liquid form, gel form, liquid + chow), HF consistently promoted greater intake and weight gain than HC. In summary, the ability of an HF diet to enhance calorie intake and weight gain relative to an isocaloric HC diet was observed across three levels of energy density; when diet form was changed to a semisolid gel; and when nutritionally complete low-fat chow was available ad libitum. These findings are consistent with previous observations [12,30] that an HF diet enhances daily kilocalorie intake and weight gain at least partly via a mechanism that is unrelated to caloric density. Acknowledgements Ladan Fakory, Joann Frazier, Karmeshia Rice, Tina Thelen-Squibb, Michelle Trappler, and Jackie Whitecavage provided excellent technical assistance. Supported by NIDDK 55367 and the Designated Research Initiative Fund, UMBC.
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[9] Holt SHA, Miller JCB, Petocz P, Farmakalidis E. A satiety index of common foods. Eur J Clin Nutr 1995;49:675 – 90. [10] Lissner L, Levitsky DA, Strupp BJ, Kalkwarf HJ, Roe DA. Dietary fat and the regulation of energy intake in human subjects. Am J Clin Nutr 1987;46:886 – 92. [11] Lissner L, Heitmann BL. Dietary fat and obesity: evidence from epidemiology. Eur J Clin Nutr 1995;49:79 – 90. [12] Lucas F, Ackroff K, Sclafani A. High-fat diet preference and overeating mediated by postingestive factors in rats. Am J Physiol 1998; 275:R1511 – 22. [13] Lucas F, Ackroff K, Sclafani A. Dietary fat-induced hyperphagia in rats as a function of fat type and physical form. Physiol Behav 1989;45:937 – 46. [14] Lucas F, Sclafani A. Hyperphagia in rats produced by a mixture of fat and sugar. Physiol Behav 1990;47:51 – 5. [15] Mela DJ, Sacchetti DA. Sensory preferences for fats: relationships with diet and body composition. Am J Clin Nutr 1991;53:908 – 15. [16] Poppitt SD, Prentice AM. Energy density and its role in the control of food intake: evidence from metabolic and community studies. Appetite 1996;26:153 – 74. [17] Rolls BJ, Bell EA, Castellanos VH, Chow M, Pelkman CL, Thorwart ML. Energy density but not fat content of foods affects energy intake in lean and obese women. Am J Clin Nutr 1999;69:863 – 71. [18] Rolls BJ, Hammer VA. Fat, carbohydrate, and the regulation of energy intake. Am J Clin Nutr Supplement 1995;62:1086S – 95S. [19] Saltzman E, Dallal GE, Roberts SB. Effect of high-fat and low-fat diets on voluntary energy intake and substrate oxidation: studies in identical twins consuming diets matched for energy density, fiber, and palatability. Am J Clin Nutr 1997;66:1332 – 9. [20] Sclafani A, Lucas F, Ackroff K. The importance of taste and palatability in carbohydrate-induced overeating in rats. Am J Physiol 1996;270:R1197 – 202. [21] Stubbs RJ, Harbron CG, Murgatroyd PR, Prentice AM. Covert manipulation of dietary fat and energy density: effect on substrate flux and food intake in men eating ad libitum. Am J Clin Nutr 1995;62:316 – 29. [22] Stubbs RJ, Harbron CG, Prentice AM. Covert manipulation of the dietary fat to carbohydrate ratio of isoenergetically dense diets: effect on food intake in men feeding ad libitum. Int J Obes 1996;20:651 – 60. [23] Van Stratum P, Lussenberg RN, Van Wezel LA, Vergroesen AJ, Cremer HD. The effect of dietary carbohydrate:fat ratio on energy intake by adult women. Am J Clin Nutr 1978;31:206 – 12. [24] Warwick ZS, Bowen KJ. Fat vs. carbohydrate foods as a portion of daily intake: effect on total kcals and weight gain. Meeting of the Society for the Study of Ingestive Behavior, Baltimore, 1997. [25] Warwick ZS, McGuire CM. Satiating effects of fat. In: Chow CK, editor. Fatty acids in foods and their health implications. 2nd ed. New York: Marcel Dekker, 2000. p. 511 – 9. [26] Warwick ZS, McGuire CM, Bowen KJ, Synowski SJ. Behavioral expression of high-fat diet hyperphagia: meal size and postprandial satiety. Am J Physiol 2000;278:R196 – 200. [27] Warwick ZS, Schiffman SS. Role of dietary fat in calorie intake and weight gain. Neurosci Biobehav Rev 1992;16:585 – 96. [28] Warwick ZS, Schiffman SS, Pappas TN, Hall WG. Taste and smell sensations enhance the satiating effect of both a high-carbohydrate and a high-fat meal in humans. Physiol Behav 1993;53:553 – 63. [29] Warwick ZS, Synowski SJ. Effect of food deprivation and maintenance diet composition on fat preference and acceptance in rats. Physiol Behav 1999;68:235 – 9. [30] Warwick ZS, Weingarten HP. Determinants of high-fat diet hyperphagia: experimental dissection of orosensory and postingestive effects. Am J Physiol 1995;269:R30 – 7.
Dietary fat content affects energy intake and weight gain independent of diet caloric density in rats Zoe S. Warwick*, Steven J. Synowski, Kimberly R. Bell Department of Psychology, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA Received 6 November 2001; received in revised form 30 April 2002; accepted 28 May 2002
Abstract Recent considerations of high-fat diet hyperphagia have focused on fat’s relatively high energy density as the critical variable which promotes overeating. However, a high-fat (HF) diet has been shown to enhance intake and weight gain relative to a high-carbohydrate (HC) diet when both energy density and palatability are equated [Am. J. Physiol. 269 (1995) R30]. The present studies investigated the generality of this finding across manipulations of diet caloric density, diet physical form, and chow availability. Separate groups of male rats were fed HF or HC at either 2.3 or 1.15 kcal/ml for 16 days; HF feeding enhanced weight gain relative to HC across both levels of energy density. HF hyperphagia also occurred when diets were presented in semisolid (gelled) form, and when chow was available in addition to liquid diet. These findings are consistent with previous observations that an HF diet can enhance daily kilocalorie intake and weight gain at least partly via a mechanism that is unrelated to caloric density. D 2002 Elsevier Science Inc. All rights reserved. Keywords: Dietary fat; Dietary carbohydrate; Caloric density; Hyperphagia
1. Introduction Consumption of a diet high in fat is often associated with greater caloric intake and weight gain than occurs on a lowfat diet. This has been revealed in epidemiological studies, via experimental manipulation of dietary fat content using human subjects, and in animal models of dietary-induced overeating (see Refs. [25,27] for reviews). However, dietary fat content has often been confounded with diet caloric density and/or palatability, making it difficult to interpret the findings in terms of a nutrient-specific effect of fat. High-fat (HF) foods have a reputation for being highly palatable, much more so than high-carbohydrate (HC) foods, and this is often taken to explain why HF diets promote hyperphagia. In humans, food fat content has been positively correlated with palatability ratings in aggregate [9], although there are marked inter- and intra-individual differences in hedonic response to increased dietary fat [15]. A role for palatability-induced enhancement of daily intake has been demonstrated in rats [20]; however, only a HC diet * Corresponding author. Tel.: +1-410-455-2360; fax: +1-410-4551055. E-mail address: [email protected] (Z.S. Warwick).
was used in this study and thus the findings do not illuminate the relative importance of palatability in determining intake of HF vs. HC diets. Evidence indicates, however, that a palatability advantage cannot completely account for HF diet-induced overeating. In one study [10], women ate diets containing either a low (15 – 20%), medium (30 –35%) or high (45 –50%) proportion of calories from fat for 2 weeks. Average daily calorie intake was positively related to dietary fat content, even though the HF diet tended to be rated as less palatable than the low-fat diet. Another study in which fat content was not systematically related to palatability also demonstrated increased caloric intake in response to increases in dietary fat content [21]. However, differences in fat content were confounded with differences in energy density, presenting an interpretive problem. Relative caloric density has been implicated in the excessive caloric intake associated with HF diets. A review [16] of human ingestive responses to manipulation of dietary fat indicates the tendency of subjects to eat a constant weight of food regardless of fat content (and caloric density), implicating mass and/or volume-related cues, such as stomach fill and/or number of bites, in the control of intake. Since fat is more calorically dense than either protein
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or carbohydrate, caloric intake and relative body weight should increase as dietary fat content and caloric density increase, as has been observed in free-living humans [11]. Epidemiological data are, however, difficult to interpret due to the covariance of dietary fat content with other dietary and lifestyle factors which affect energy balance. Controlled feeding studies demonstrate that simultaneous increases in dietary fat content and caloric density do enhance energy intake [6,10,21]. Additional evidence for the role for diet caloric density in intake regulation comes from studies in which dietary fat content was manipulated while keeping the caloric density of the diet constant; calorie intake did not differ across the various levels of fat [17,19,22,23]. The independent effects of dietary fat and energy density have been assessed directly in a series of experiments by Rolls et al. [1,2,17], who measured the effect of manipulating the fat content and energy density of foods on intake by women. Importantly, the palatability of all foods was similar. Subjects consumed fewer calories when the foods had lower energy density; fat content did not affect intake. A review of 40 animal studies [27] comparing energy regulation on HF vs. low-fat diets indirectly revealed the role of diet caloric density in hyperphagia. Of the studies in which the caloric density of the diets was similar (density of HF no more than 25% greater than HC, accomplished by dilution of the HF diet with inert material), greater weight gain by HF-fed rats relative to HC-fed rats was observed in only 5 out of the 10 studies. In contrast, when the caloric density of the HF diet markedly exceeded that of the HC diet (density of HF at least 25% greater than HC), 28 out of 30 studies observed greater weight gain by the HF-fed rats. However, because all diets were consumed orally, interpreting the results is problematic. The more calorically dense HF diets may have promoted greater weight gain because they were more palatable, produced less stomach distention per kilocalorie, and/or less potently stimulated pre- or postabsorbtive satiety signals. Together, these findings implicate HF foods’ caloric density, and potentially their palatability, as relevant attributes which promote overeating. However, the lack of HF diet overeating observed in studies in which energy density and palatability were controlled [2,19,22,23] does not imply that the nutrient-specific effects of fat play no role in promoting hyperphagia. Indeed, the hyperphagic effect of dietary fat, independent of energy density and palatability, has been demonstrated in animal studies. In a self-regulated intragastric feeding paradigm, rats infused either HF or HC liquid diets having identical energy density over 16 days. Since the diets were not tasted, the greater intake by rats infusing the HF diet directly demonstrated that the unique postingestive effects of fat can promote hyperphagia [30]. Subsequently, Lucas et al. [12] replicated this finding using a within-subjects paradigm. Studies focusing on short-term controls of feeding (meal size and postprandial satiety) have also demonstrated that increasing food fat content is often associated with larger meal size (reduced satiation) and with
greater subsequent intake (reduced postprandial satiety) (reviewed in Ref. [25]). The purpose of the present studies was to further investigate the hyperphagia induced by an HF diet that is isocaloric with an HC diet. Specifically, the generality of the phenomenon across manipulations of diet caloric density, diet physical form, and chow availability was examined. In Experiment 1, diet composition and caloric density were independently manipulated. Experiment 2 assessed the effect of changing the physical characteristics of the diets to a semisolid gel, as evidence suggests that the physical form of diets can affect intake [13]. Experiment 3 addressed the question of whether HF diet hyperphagia would persist even when a low-fat, nutritionally complete food (chow) was also available ad lib.
2. General methods 2.1. Animals and housing Male Long – Evans rats were individually housed in hanging wire mesh cages, with ad lib powdered chow (Purina 5001 Rodent chow, 3.3 kcal/g: 28% kcal from protein, 60% kcal from carbohydrate, 12% kcal from fat) and water except as noted. A 12:12 light/dark cycle was maintained. 2.2. Diets Liquid HF and HC diets, isocaloric at 2.3 kcal/ml, were prepared as described previously [30] using tap water, with the addition of micronutrients, which were dissolved in a small quantity of water prior to being added to the milk. (To permit their use in intragastric infusion paradigms as well as oral feeding studies [26,30], the protein content of these diets must be low, but in all other respects they are nutritionally complete.) Ingredients and macronutrient composition are listed in Table 1. Diluted versions of these diets were obtained by mixing appropriate volumes of diet and Table 1 Diet composition
Evaporated milk (ml) Sucrose (g) 44.4% corn oil emulsion (ml) Vitamin mixa (g) Mineral mixb (g) Water kcal/ml % kcal from fat % kcal from carbohydrate % kcal from protein a b
High-fat
High-carbohydrate
540 140 250 5.98 8.13 to bring volume to 1 l 2.3 60 33 7
540 390 – 5.98 8.13 to bring volume to 1 l 2.3 17 76 7
Lieber – Dicarli liquid diet vitamin mix (Dyets). Modified AIN-93G mineral mix (Dyets).
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tap water. Diets were presented in plastic bottles with rubber stoppers and stainless steel ball spouts. 2.3. Experiment 1: caloric density manipulation The purpose of this study was to determine whether diet caloric density affected the magnitude of overeating and weight gain associated with the HF liquid diet. 2.3.1. Method Forty rats (age 73 days) were divided into four weightmatched groups (mean body weight 315 g). Each group received one of the following diets as the sole source of nutrition for 16 days: HF at 2.3 kcal/ml, HF at 1.15 kcal/ml, HC at 2.3 kcal/ml, HC at 1.15 kcal/ml. Intakes were measured daily by weighing the food bottles to the nearest gram, and animals were weighed periodically. 2.3.2. Results Rats consuming the HF diet at 2.3 kcal/ml had greater daily intake (mean 120.6, S.E. 9.02 kcal) than rats consuming HC at 2.3 kcal/ml (mean 97.2, S.E. 6.08 kcal), t(18) = 2.15, P < .05. Due to leakage problems, reliable intake measurements could not be obtained for the diluted (1.15 kcal/ml) diets. The HF diets promoted greater body weight gain than the HC diets, independent of diet caloric density (Fig. 1). Statistically, this was reflected by a main effect of diet [ F(1,38) = 5.05]. Neither the main effect of density nor the Diet Density interaction was significant. 2.3.3. Discussion The HF diet promoted greater caloric intake and weight gain than the HC diet, consistent with previous findings [30]. Although kilocalorie intake of the diluted diets could not be measured, the similarity of weight gain within each diet type, irrespective of diet density (Fig. 1), suggests that rats fed the diluted diets consumed approximately the same
Fig. 1. Experiment 1. Body weight gain across 16 days for rats fed HF or HC at either 2.3 or 1.15 kcal/ml. Values are means ± S.E.M.
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daily kilocalorie as their counterparts fed the full-strength diets. To further explore the role of diet caloric density in intake and weight gain, 14 additional animals were divided into two weight-matched groups (mean body weight 360 g) and fed either HF or HC at an even lower density (0.575 kcal/ml) for 16 days. Food intake could not be measured reliably due to leakage problems. It is important to note that these rats had a higher starting body weight than animals consuming the more calorically dense diets and thus actual weight gains cannot be directly compared to the 2.3- and 1.15-kcal/ml groups. However, the macronutrient effect was again observed: rats fed HF gained more weight (mean 42.3, S.E. 3.97 g) than rats fed HC (mean 28.0, S.E. 4.40 g), t(12) = 2.41, P < .05. 2.4. Experiment 2: semisolid HF and HC diets Experiment 1 and previous findings [30] demonstrate that the liquid HF diet reliably increases caloric intake and weight gain relative to the liquid HC diet, and this effect persists even when diet energy density is decreased. HF and HC were originally developed in liquid form to permit the use of sham and intragastric feeding techniques to isolate orosensory and postingestive controls of feeding, respectively [30]. However, calories are not customarily ingested entirely in liquid form, and so it is important to ascertain whether HF hyperphagia generalizes beyond the liquid format. There is evidence that the physical form of the diet can affect intake: rats ate less of a fat option when presented in gel form relative to liquid emulsion [13]. The goals of Experiment 2 were twofold: to investigate whether HF elicited hyperphagia relative to HC when the diets were presented in semisolid form, and to obtain accurate measurements of intake of the diluted diets. 2.4.1. Method Seventeen rats (age 112 days) were divided into two weight-matched groups (mean body weight 438 g). Each group received either semisolid (gelled) HF or HC (both at 1.15 kcal/ml) as the sole source of nutrition for 16 days. The gelled diets were prepared in the same manner as the liquid diets, with the following modifications. The water used to dissolve micronutrients was first heated to 80 °C. After the micronutrients had dissolved, 10 g of gelatin (Dyets, Bethlehem, PA) per liter of finished diet was added. When this had dissolved (approximately 5 min), diet preparation proceeded as described above. The finished diets were poured into stainless steel food cups and refrigerated for at least 3 h. Intakes were measured daily and animals were weighed periodically. 2.4.2. Results Rats fed the semisolid HF diet had greater intake (mean 119.0, S.E. 4.18 kcal/day) than rats fed the semisolid HC diet (mean 104.9, S.E. 4.35 kcal/day), t(15) = 2.89, P < .05
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(Fig. 2). Weight gain paralleled the difference in intake, with HF-fed rats gaining more weight than rats fed HC, t(15) = 2.35, P < .05 (Fig. 3). 2.4.3. Discussion When presented in semisolid (gelled) form, the HF diet promoted greater kilocalorie intake and weight gain than the HC diet, consistent with results obtained when these diets were liquids (Experiment 1; Ref. [30]). Because animals consuming the gel diets were not equivalent in terms of body weight to rats consuming the liquid diets, absolute weight gains cannot be compared across the two diet forms. Growth on the gel version of the 1.15-kcal/ml diets (Fig. 2) was more rapid than on the liquid versions (Fig. 1), possibly due to the different starting weights or to the greater protein fraction in the gel diets. Gelatin improved the protein fraction of the diets by about 50% (from 7% kcal in liquid diets to 10% kcal in gel diets). Daily intake of the gel diets may also have been slightly higher than their liquid counterparts since the gel was apparently more palatable; subsequent overnight two-choice tests with different animals (n = 8 per diet) revealed a clear preference for the gelled version over the liquid (HF mean intake of gel = 106.8 g, of liquid = 22.4 g; HC mean intake of gel = 64.3 g, of liquid = 26.0 g). 2.5. Experiment 3: liquid diets plus chow Experiments 1 and 2 verified the hyperphagia-promoting effect of the HF diet. However, in these studies, the liquid/ gelled diets were the sole nutrient source, which does not accurately model realistic eating in which a variety of both HF and low-fat foods are available. It is possible that the availability of a nutritionally complete low-fat food might attenuate the hyperphagia observed when HF is the sole source of nutrition. Therefore, a study was conducted in
Fig. 2. Experiment 2. Daily caloric intake averaged over 4-day blocks for rats fed gelled HF or HC. Values are means ± S.E.M.
Fig. 3. Experiment 2. Body weight gain across 16 days for rats fed gelled HF or HC. Values are means ± S.E.M.
which rats received ad lib powdered chow in addition to liquid diet. 2.5.1. Method Nineteen rats (age 53 days) were divided into two weight-matched groups (mean body weight 247 g). Each group received either HF or HC ad lib (both at 2.3 kcal/ml), in addition to ad lib chow. Intakes of chow and of liquid diet were measured daily and animals were weighed periodically. 2.5.2. Results Rats given HF consumed more liquid diet (mean 113.7, S.E. 5.05 kcal) than rats given HC (mean 70.0, S.E. 5.71 kcal), t(17) = 5.75, P < .001. Chow intake of HF-fed rats (mean 40.6, S.E. 3.42 kcal) was slightly lower than HC-fed rats (mean 49.9, S.E. 8.0 kcal), although this difference was not statistically significant. Thus, total daily kilocalorie intake (liquid diet + chow) was greater for rats fed HF (154.3, S.E. 6.69 kcal) than for rats fed HC (119.9, S.E. 3.95 kcal), t(17) = 4.30, P < .001 (Fig. 4).
Fig. 4. Experiment 3. Daily caloric intake averaged over 4-day blocks for rats fed chow and either HF or HC. Values are means ± S.E.M.
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Fig. 5. Experiment 3. Body weight gain across 16 days for rats fed chow and either HF or HC. Values are means ± S.E.M.
Body weight gain was rapid in all rats and was greater in HF-fed rats (avg 161.9, S.E. 15.3 g) than in HC-fed rats (avg 136.7, S.E. 12.5 g), although the difference did not reach statistical significance (Fig. 5). 2.5.3. Discussion The greater total kilocalorie intake (chow + liquid diet) by rats given HF vs. isoenergetic HC further illustrates that consuming a food high in fat increases total daily intake even when it is accompanied by a nutritionally complete, familiar food (chow) available ad libitum. These findings are consistent with another study which examined shortterm (22 h) energy intake in rats who self-infused either HF or HC while consuming chow ad libitum. Infusion of HF exceeded HC while chow intakes did not differ: thus total kilocalorie intake was greater on the HF infusion days [12].
3. General discussion A diet high in fat enhances daily caloric intake relative to a low-fat diet at least partly via a mechanism that is independent of caloric density. When HF and HC liquid diets were formulated to have equivalent caloric density, HF elicited greater intake when diets were consumed orally either with (Expt. 3) or without [30] ad lib chow; when diets were intragastrically infused either with [12] or without [30] ad lib chow; and when diets were gelled to semisolid form (Expt. 2). Dietary dilution did not negate the impact of high dietary fat; weight gain of HF-fed rats exceeded that of HCfed rats across three levels of diet caloric density (Expt. 1). These findings are consistent with analyses of acute (short-term) ingestive behavior in rat, which have demonstrated that meal size in terms of kilocalories is greater when HF is consumed relative to isoenergetic HC [26,29]. A preload of HF was less suppressive of subsequent intake (less satiating) than an isocaloric preload of HC, as indicated by relatively larger test meal intake following HF [26].
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Direct evidence that dietary fat can be less satiating than carbohydrate when chronically consumed in addition to chow comes from a study in which fixed quantities of either fat or carbohydrate were consumed, and spontaneous intake of chow measured. Rats consuming 30 ml/day of liquid diet in addition to chow ate more chow and thus more total kilocalories when given HF compared to HC [24]. Burggraf et al. [3] observed that intragastric infusion of fat, approximating 36% of baseline kilocalorie intake, suppressed oral intake less than isocaloric infusion of glucose. However, human preloading studies have yielded inconsistent findings regarding the relative satiety produced by fat vs. carbohydrate (reviewed in Refs. [18,25]). While some studies have found fat to produce less postprandial satiety than carbohydrate, in other instances, test meal intake following HF and HC preloads was similar (e.g. Refs. [5,8,28]). The test meals used in the latter studies may not have had appropriate sensitivity to detect macronutrient effects. A multi-item test lunch of familiar foods [28] elicited relatively high intake (approximately 1480 kcal), as did sweet, presumably novel liquid test meals (approximately 861 and 1177 ml in Refs. [5,8]), thus raising the possibility of a ceiling effect on intake. Since no-preload conditions were not run, this cannot be verified (although slight compensation for caloric vs. noncaloric preloads was observed in Ref. [8]). Human responsivity to macronutrients is complex and reflects the combined influence of sensory, postingestive, cognitive, and situational/methodological influences [4,18]. When liquid diets were available as an option in addition to chow, HF promoted greater total intake (chow + diet) than isoenergetic HC (Expt. 3; Ref. [12]). Previous observations of hyperphagia elicited by HF options relative to HC options have not dissociated macronutrient and caloric density effects [14]. Two pieces of evidence indicate that the greater intake of HF cannot be attributed to a palatability advantage. Intakes of HF and HC are similar in one-bottle sham-feeding tests [30], and more HF than HC is infused in a self-infusion paradigm in which diets are not tasted [12,30]. The mechanism(s) by which dietary fat promotes greater caloric intake is unknown but may relate to differences between the actions of fat and carbohydrate both pre- and postabsorbtively. Intragastric infusion of nutrient more effectively suppressed spontaneous food intake than an intravenous infusion; under both conditions, fat infusion was less suppressive than carbohydrate [3]. The relative proximity of the liver to the entry of energy substrates into the bloodstream may also be relevant, as the liver is implicated as a source of satiety signals [7]. Fat is absorbed into the lacteals and thus bypasses the liver while carbohydrates are absorbed into the portal vein. Daily kilocalorie intakes in Experiments 1 and 2 for rats HF-fed were approximately 120 kcal, and for rats fed HC were approximately 101 kcal, yet absolute weight gains in each diet group were greater in Experiment 2. This difference in weight gain was probably attributable to the increased
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protein content of the gel diets (Experiment 2) relative to the liquid diets (Experiment 1). Similarly, consumption of highprotein chow in addition to liquid diet (Experiment 3) no doubt facilitated growth. HF diets can promote weight gain that is disproportionally high relative to the increased caloric intake; indeed, weight gain on an HF diet can exceed that on an HC diet despite equivalent caloric intake [27]. The important observation is that across three feeding paradigms (liquid form, gel form, liquid + chow), HF consistently promoted greater intake and weight gain than HC. In summary, the ability of an HF diet to enhance calorie intake and weight gain relative to an isocaloric HC diet was observed across three levels of energy density; when diet form was changed to a semisolid gel; and when nutritionally complete low-fat chow was available ad libitum. These findings are consistent with previous observations [12,30] that an HF diet enhances daily kilocalorie intake and weight gain at least partly via a mechanism that is unrelated to caloric density. Acknowledgements Ladan Fakory, Joann Frazier, Karmeshia Rice, Tina Thelen-Squibb, Michelle Trappler, and Jackie Whitecavage provided excellent technical assistance. Supported by NIDDK 55367 and the Designated Research Initiative Fund, UMBC.
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