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Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, PA 16802-6504
2To whom correspondence should be addressed. E-mail: dms493{at}psu.edu.
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ABSTRACT |
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 TOP ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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0.008) than intakes of rats tested on HHF. HHF-tested rats did not differ in body weight by the end of wk 2 of testing. In a subsequent short-term choice preference test, rats exhibited an equal relative preference for HHF irrespective of their maintenance diets (HF = 63.1%, LF = 68.1%, P = 0.29). Finally, we examined the effect of intraperitoneal NaCl or cholecystokinin (CCK)-8 (100 and 250 ng/kg) injection on 1-h food intake. Both doses of CCK significantly suppressed food intake in LF-fed rats but not HF-fed rats. These results demonstrate that chronic ingestion of a HF diet leads to short-term overconsumption of a high-energy, high-fat food compared with LF-fed cohorts, which is associated with a decreased sensitivity to CCK.
KEY WORDS: • dietary fat • satiation • obesity • energy density • appetite
Prolonged ingestion of a high-fat (HF)3 diet is associated with overconsumption and obesity (1), but the underlying mechanisms are still not clear. Satiation, the physiological process of meal termination, is mediated predominantly by feedback signals arising from the gastrointestinal tract. One possibility is that fat-induced satiation mechanisms might be altered in response to chronic fat ingestion such that their sensitivity or efficacy is diminished. Deficits in satiation signals are strongly suspected of accompanying obesity, if not of contributing to its pathogenesis in both humans (2) and rats (3,4). One such satiation signal is cholecystokinin (CCK), whose effects on food intake are diminished in rats adapted to a HF diet (5).
The gut peptide CCK inhibits food intake by reducing meal size when administered exogenously (6). CCK is released predominantly from I cells in the small intestine in response to the presence of fat or protein and elicits multiple effects on the gastrointestinal system, including the regulation of gut motility, gastric emptying, gastric acid secretion, contraction of the gallbladder, and pancreatic enzyme secretion (7,8). Moreover, decades of investigations have documented CCK as one of the most biologically potent satiety peptides controlling food intake (9). Plasma CCK concentrations are elevated in response to intraintestinal products of fat digestion, unhydrolyzed protein, and inhibitors of pancreatic trypsin, but are not elevated by intraintestinal carbohydrates (10–12). Accordingly, ingestion of a low-fat (LF) diet stimulates very little CCK secretion into plasma, whereas HF and LF-high-protein (HP) diets markedly increase plasma CCK concentrations (11,13). Persistently elevated plasma CCK, accompanying long-term HF diet consumption, leads to several adaptive changes in nutrient- and CCK-signaling pathways. For example, relative to rats fed a LF diet, rats fed a HF diet exhibit increased pancreatic secretory and plasma CCK responses to intestinal fat (14). Rats fed a HF diet also secrete reduced amounts of pancreatic amylase in response to CCK (15) and secrete increased amounts of pancreatic lipase (14,16). Although there has been considerable progress in our understanding of how gastrointestinal feedback signals participate in satiation, little experimental attention has been paid to the possibility that diet-induced alterations in the response to gastrointestinal signals may result in disordered food intake.
We showed previously that exogenous administration of CCK in rats fed HF or HP diets suppressed food intake markedly less than in rats fed an isoenergetic LF diet (17). Similarly, reduced sensitivity to the anorectic effects of acute CCK injection was also demonstrated in rats receiving chronic infusion of CCK via osmotic minipump (17). A reduction in sensitivity to satiation signaling in HF-fed rats is not limited to CCK. Rats fed HF diets exhibit diminished sensitivity to satiation by intestinal infusion of the fat digestion product, oleic acid, but not the sugar, maltotriose (18). These findings suggest that chronic consumption of diets high in fat actually reduces the ability of dietary fat to inhibit further food intake.
The potential participation of satiation deficits in obesity was highlighted recently with the demonstration that Otsuka Long Evans Tokushima fatty (OLETF) rats, which do not express CCK type-1 (CCK-1) receptors, overeat and become obese (4). Several laboratories (19,20), including our own (21), demonstrated that OLETF rats do not reduce their food intake in response to systemic injections of CCK or intestinal nutrients. In addition, rats of another genetically obese strain, the Zucker fatty rats, exhibit reduced satiation in response to exogenous CCK, compared with lean controls (22,23). These rats also exhibit apparent reduced responses in other systems that are controlled by CCK, including leptin and insulin (24,25). The implications of reduced CCK sensitivity on overeating and body weight gain have not been addressed despite abundant evidence demonstrating that rats overeat when fed a HF diet (1,26–28). Therefore, the first aim of the present study was to test the hypothesis that maintenance of a HF diet promotes overconsumption of a high-energy, high-fat (HHF) food.
Although rats fed HF diets selectively increase their acceptance of oil within discrete short-term tests (29), there is also some evidence that the composition of the maintenance diet influences dietary preference (30). Therefore, it is unclear whether rats accustomed to consuming increased amounts of fat demonstrate an increased preference (when a choice among foods is offered) for a HHF food. Thus, the second aim of these studies was to assess the relative preference for a HHF diet in both HF- and LF-maintained rats. Finally, to evaluate whether overconsumption of a HHF food by HF-maintained rats is accompanied by decreased sensitivity to satiation signaling, inhibition of feeding by exogenous CCK was measured in both HF- and LF-maintained rats.
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MATERIALS AND METHODS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Adult male Sprague-Dawley rats (Harlan) weighing 250–350 g at the start of the experiments were housed individually in hanging wire-bottomed cages and adapted to a 12-h light:dark cycle (lights on at 0600 h) in a temperature-controlled vivarium. Water was freely available throughout the experiments, and body weight was recorded daily. This protocol was approved by The Pennsylvania State University Institutional Animal Care and Use Committee.
Diets
After 1 wk of free access to a pelletized rodent diet (Purina, 5001), rats were divided into 2 groups matched for body weight and switched to 1 of 2 isoenergetic (16.2 kJ/g), semipurified diets (Table 1), low-fat (LF, n = 12) or high-fat (HF, n = 12). As demonstrated by our earlier studies, rats fed HF diets do not invariably exhibit excess weight gain relative to LF-fed rats because the energy density of the HF and LF diets is equivalent (5,18,31). Diets were prepared in our laboratory from commercially available macronutrient sources (Bio-Serv, ICN Biomedicals, and Sigma Chemical) and were used as both maintenance and test diets, as specified in the experimental protocols. All diets were presented in spill-resistant glass jars that were secured onto the inside front of the home cage by a stainless steel clip. Fresh food was provided every day and removed only for weighing and during experiments as specified below.
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Experiment 1: Rats fed high-fat diets exhibit hyperphagia of a high-energy food. Rats were adapted to their respective maintenance diets (HF or LF) for 3 wk before testing began. This 3-wk adaptation period was shown previously by our laboratory to be sufficient for the development of reduced sensitivity to CCK in HF-fed rats (5,18,31); during this time, body weight gain of rats fed the LF and HF diets was equal (5,18). On each test day, maintenance diets were removed and weighed at 0800 h. At noon, after a brief 4-h period of food deprivation, 6 rats from each dietary group received a preweighed amount of the HHF diet; the remaining 6 rats from each group received a preweighed amount of their own maintenance diet (i.e., controls). Therefore, a total of 4 experimental groups based on maintenance diets and the diets presented during the 3-h short-term tests were included: LF/HHF, HF/HHF, LF/LF, and HF/HF. Food intake was measured (accounting for spillage) at 1, 2, and 3 h after diet presentation. At the end of h 3, all diets were removed and fresh maintenance diets were returned to all rats. Testing occurred daily for 15 consecutive days during which rats were continually exposed to the same diet.
Experiment 2: Relative preference for the high-energy food (HHF) in rats fed high-fat or low-fat diets. Rats used in Expt. 1 consumed their respective LF and HF maintenance diets and were not exposed to any experimental condition for 2 wk. To prevent neophobia before the initiation of preference testing, all rats were given overnight access to each of the 3 diets (LF, HF, or HHF) on 2 different occasions ("diet exposure"). Each test diet was presented from 1700 h until 0800 h the next day (a total of 15 h) for 2 consecutive days, with at least 48 h elapsing between each new diet exposure. The position (left/right) of the same test diet was randomized and switched between the 2 d of exposure, and the order of presentation of the diets was assigned such that one-third of the rats were fed 1 of the 3 diets on any given overnight diet exposure. During overnight diet exposures, only the specific diet being exposed was available. The jars were placed on the side of the home cage opposite that on which rats received their maintenance diets to prevent possible location bias. Fresh maintenance diets were placed back in their regular location within the cage when rats were not undergoing diet exposure.
On d 3 after the last overnight diet exposure, 3-h 2-choice preference testing began. For all rats, 3 different diet pairings were tested: HHF vs. HF, HHF vs. LF, and HF vs. LF. Each pair of diets was tested on 2 consecutive days with the position (left/right) of the diets randomized and alternating each test day. At least 40 h elapsed between each of the 3 pairs of tests. Rats were assigned to different sequences of diet pairings so that one-third of the rats within the same maintenance-diet group received the same pair of diets during any preference test. On the days preference testing was conducted, maintenance diets were removed at 0800 h and preference testing began at noon. This brief deprivation schedule was identical to that used in Expt. 1. The intake of each diet (adjusting for spillage) was measured at the end of each hour during the 3-h testing period. Similar to diet exposure, preference-test diet jars were placed on the side of the home cage opposite that on which rats received their maintenance diets; fresh maintenance diets were returned immediately upon conclusion of the testing session. Body weight and 24-h intake were measured throughout the entire experiment. The protocol used was similar to that of other published studies examining dietary preferences (32).
Experiment 3: Reduced sensitivity to CCK in rats fed high-fat diets. This experiment examined the suppression of food intake in response to an acute i.p. injection of CCK octapeptide, sulfated (CCK; American Peptide). Upon conclusion of Expt. 2, rats continued to consume their respective LF and HF maintenance diets for 1 wk, during which time no experimental manipulations occurred. The testing procedure used in this experiment is similar to that used previously by our laboratory (5,33), with the exception of the food-deprivation schedule. Instead of testing sensitivity to CCK in rats deprived of food overnight, the same 4-h deprivation used in Expts. 1 and 2 was employed here. Briefly, maintenance diets were removed at 0800 h and each rat was weighed. At noon, rats were injected i.p. (1.0 mL/kg) with either sterile NaCl or CCK. Maintenance diets were returned 5 min after the injection, and intake was recorded at the end of 1 h. The satiating effect of CCK was investigated for 2 doses (100 and 250 ng/kg), with all rats administered the same dose on a given test day. These tests were conducted on consecutive days, and each dose of CCK was tested twice. One test of intake after 0.9% NaCl was followed by 1 test after CCK.
Statistical analysis
In Expt. 1, rats were assigned to 1 of 4 experimental groups based on maintenance and test diet (LF/HHF, HF/HHF, LF/LF, and HF/HF). Mean intakes for each rat were subjected to 2-way repeated measures ANOVA (rmANOVA), with experimental group and time as independent variables. Mean intakes of exposure diets in Expt. 2 were subjected to 2-way rmANOVA, with maintenance and exposure diet as independent variables. For preference-test data, paired-samples t tests did not reveal a significant side preference for any of the diet pairings; therefore, the left- and right-side intakes for each diet within a pair of preference tests were pooled for further analysis. Mean intake at each time point for each rat was subjected to 2-way rmANOVA, with maintenance diet and preference-test diet as independent variables. To determine relative preferences, the total amount consumed for each diet was divided by the total amount of all diets consumed across all preference tests, and multiplied by 100 to yield a percentage. Data for Expt. 3 are expressed as the percentage suppression of 1-h food intake for each rat, which was obtained using the following formula: % suppression = 100 (intake after saline – intake after peptide)/intake after saline. Raw intakes of maintenance diets for each rat were subjected to 2-way rmANOVA, with maintenance diet and injections as independent variables. All analyses were conducted using PC-SAS (version 8.02, SAS Institute). Differences among group means (adjusted) were analyzed using Tukey-Kramer multiple post-hoc comparisons, with P < 0.05 considered significant.
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RESULTS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Beginning on d 2, and continuing through d 15, HF/HHF rats consumed more food than any other group when intake of the test diet was measured at 1 h (
1.7 g; P 0.008), 2 h (2.0 g; P 0.011), and 3 h (2.2 g; P 0.016, Fig. 1A). The 3-h test intake did not differ between d 1 and 15 for any group (data not shown). By the end of the 3-h test period, HF/HHF rats consumed a mean of 47.7 kJ more than LF/HHF rats (P < 0.005), and 119.6 kJ more than HF/HF rats (P < 0.001, Fig. 1B and Fig. 2). In contrast, HF/HHF rats consumed the least amount of their maintenance diet after the 3-h test session (minimum mean difference of 61.5 kJ compared with LF/HHF, P < 0.004), resulting in a 24-h energy intake similar to all other groups (Fig. 2). LF/HHF rats, on the other hand, consumed more energy than either LF/LF (P < 0.029) or HF/HF rats (P < 0.015), but not HF/HHF rats (P = 0.99). Upon conclusion of the 15-d testing period, body weight gain did not differ between HF/HHF rats and their respective control (HF/HF) group (P = 0.19, Fig. 3). Conversely, LF/HHF rats gained more weight than LF/LF rats (P < 0.001). Body weight did not differ between LF/HHF and HF/HHF rats at any point during the experiment (P = 0.99).
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Overnight diet exposure. During overnight diet exposures, HF-maintained rats consumed the greatest amount of HHF diet compared with LF-maintained rats (17.6 ± 0.2 vs. 15.8 ± 0.6 g, P = 0.047). HF-maintained rats also consumed more HF diet than LF-maintained rats (14.1 ± 0.5 vs.10.8 ± 0.9 g, P < 0.001). HF- and LF-maintained rats did not differ in consumption of LF diet (13.7 ± 0.5 vs. 13.0 ± 0.4 g, P = 0.9).
Preference testing. During preference testing, rats were presented with all 3 different diet pairings (HHF vs. HF, HHF vs. LF, and HF vs. LF) on 2 occasions. When LF-maintained rats were presented with LF and HHF diets concurrently, they consumed 0.7 ± 0.2 g of the LF diet and 6.4 ± 0.3 g of the HHF diet within the 3-h test intake period. Similarly, HF-maintained rats presented with the same choice consumed 1.9 ± 0.3 g of the LF diet and 6.2 ± 0.4 g of the HHF diet. When LF-maintained rats were presented with HF and HHF diets, they consumed 0.3 ± 0.1 g of the HF diet and 6.8 ± 0.4 g of the HHF diet. Similarly, HF-maintained rats presented with this diet choice consumed 0.1 ± 0.0 g of the HF diet and 8.2 ± 0.3 g of the HHF diet. Finally, when LF-maintained rats were presented with LF and HF diets, they consumed 3.7 ± 0.2 g of the LF diet and 1.5 ± 0.3 g of the HF diet. Rats fed HF consumed 6.3 ± 0.4 g of the LF diet and 0.4 ± 0.2 g of the HF diet. The relative preference did not differ among 1, 2, and 3 h; therefore, only the cumulative 3-h intake is presented. Although relative preference for the HF and LF diets differed between the 2 maintenance diet groups, all rats exhibited the greatest relative preference for the HHF diet, which did not differ between the 2 groups (HF = 63.1%, LF = 68.1%; P = 0.29; Fig. 4).
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Injections of CCK suppressed 1-h food intake in response to both doses tested in LF-maintained rats (% suppression, 100 ng/kg: 17.1 ± 4.4, P < 0.001; 250 ng/kg: 25.1 ± 3.7, P < 0.001, Fig. 5). In contrast, HF-maintained rats did not suppress intake after acute injection of either 100 ng/kg (1.5 ± 4.9%, P = 0.99) or 250 ng/kg CCK (6.5 ± 4.2%, P = 0.48).
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DISCUSSION |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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The duration of testing might have allowed the rats to learn to consume a more palatable food when it was offered and then reduce intake of the HF maintenance diet. However, because all groups consumed similar quantities of their respective test meal throughout the entire 15-d testing period, it is unlikely that familiarity with the daily testing schedule influenced the outcome of this study. It is also reasonable to suggest that the overconsumption of the HHF diet exhibited by the HF-fed rats may have been due in part to low acceptability of their own maintenance diet as a result of its high-fiber, low-carbohydrate composition. However, HF-fed rats presented with their own maintenance diet during testing consumed similar quantities compared with LF-fed rats tested on the LF diet, indicating that the acceptability (when only 1 diet is presented) of the 2 maintenance diets was equal. Preference testing in our 2nd experiment did in fact demonstrate that both LF and HF groups preferred the LF to the HF diet, which is indicative of the reduced palatability of the HF diet. The reason for this preferential intake of the LF diet is not immediately clear, and it might be due to its more appealing sensory properties. However, when compelled to consume the HF diet in a no-choice situation, daily intake was similar to that of rats consuming the LF diet, indicating that, despite the palatability disadvantage of the HF diet, a similar intake was produced by the postingestive effects of the HF diet. Several earlier findings support the hypothesis that the postingestive effects of fat are a primary determinant of hyperphagia (3,34). It is worth noting here that when naïve (laboratory diet–fed) rats were presented with both HF and LF diets as a choice, there was no difference in intake during the 3-h test (data not shown). In light of the fact that in Expt. 1, rats were fed either their own maintenance diet or the HHF diet, but never their opposite group’s maintenance diet, the most relevant preference pairing that has a direct bearing on our main findings reported in Expt. 1 is the choice between the rats’ own maintenance diet and the HHF diet (LF vs. HHF for LF-maintained group and HF vs. HHF for HF-maintained group). As these data reveal, both groups clearly preferred the HHF diet, whereas intake of the maintenance diet was negligible (<1 g). These results are important because they demonstrate that preference for the HHF diet was comparable in 2 groups when the maintenance diet was concurrently available, and they replicate the findings from our first experiment. Whether overconsumption of the HHF diet is a function of sensory effects vs. postingestive effects warrants further investigation.
We contend that the HHF hyperphagia in this study resulted primarily from diminished satiation signaling subsequent to HF maintenance. In support of this, our laboratory demonstrated previously that rats chronically fed HF diets exhibit diminished sensitivity to satiation by intestinal infusion of the fat digestion product, oleic acid (18). Comparable outcomes were reported in humans fed diets high in fat. Specifically, subjects consuming a HF diet for 2 wk significantly increased their mean daily food consumption, had elevated plasma CCK levels in response to a test meal, and reported subjective feelings of increased hunger and declining fullness (35). Similarly, human subjects also reported greater hunger during a lipid infusion after a 2-wk HF adaptation period (36). These data suggest that consumption of diets high in fat reduces the ability of fat to inhibit further food intake and may account for the HHF hyperphagia observed in the current study. Diminished sensitivity to suppression of food intake by intestinal fat infusion is also accompanied by decreased inhibition of gastric emptying after duodenal fat infusion in rats (31), as well as humans (37). This decreased inhibition of gastric emptying effectively results in an increased passage of fat from the stomach to the small intestine, and may be one of the mechanisms involved in the HHF hyperphagia exhibited by the HF-maintained rats. Reports by several laboratories indicate that HF diet maintenance also promotes the capacity of the gastrointestinal tract to digest and absorb fats. Physical alterations of the small intestine, including shorter and thicker microvilli, an increase in the number of enterocytes per villus, hypertrophy, and increases in mucosal protein content were reported in response to dietary fat adaptation (38). Fat adaptation also involves an increased production of hydrolytic enzymes and transporters, as well as more efficient absorption of dietary loads of fat (38). Apolipoprotein A-IV (apo A-IV) is one such factor that is stimulated by dietary lipid; it plays an important role in the integrated control of digestive function and ingestive behavior. Evidence for the adaptation of plasma apo A-IV in response to prolonged fat feeding shows that jejunal apo A-IV synthesis is increased in rats (39). Collectively, these adaptive changes indicate that the ability of the gastrointestinal tract to digest and absorb lipids is increased, and suggest that a more efficient process of lipid assimilation may also promote excessive ingestion of fat similar to the hyperphagia observed in our study.
Adaptive changes in response to chronic elevations of dietary fat are not limited to more efficient absorption of dietary loads of fat. The endogenous release of CCK and pancreatic exocrine secretion also increase in response to duodenal fat infusion in rats adapted to a HF diet compared with rats fed a LF diet (14). In line with this, our laboratory demonstrated that chronic HF diet consumption results in reduced sensitivity to peripheral administration of CCK compared with rats fed LF diets (5,17,33). In agreement with these previous reports, Expt. 3 revealed that rats fed HF diets suppressed their food intake significantly less after CCK injection than rats that were fed a LF ration. Moreover, these findings extend to our current design in rats that were food deprived for only 4 h, as opposed to the overnight deprivation period used in our previous studies. We reason that HF diet maintenance promotes overeating by reducing sensitivity to important feedback signals and consider the HHF hyperphagia exhibited by HF-maintained rats in our study to result in part from a reduced sensitivity to endogenous CCK.
Reduced sensitivity to intestinal lipid infusion (18) and CCK injection (5) in rats fed HF diets was shown previously to be specifically dependent on the fat content of the diet and was not influenced by the dietary fiber or carbohydrate content. Specifically, rats fed a HF diet exhibited diminished CCK sensitivity even when tested on consumption of a LF diet (5), and rats fed a high-fat, low-fiber diet exhibited diminished CCK sensitivity comparable to that in rats fed a high-fat, high-fiber diet (5). Furthermore, we (18) as well as others (29) reported that HF-maintained rats exhibited reduced inhibition of food intake in response to fats but not carbohydrates. These studies support the hypothesis that long-term consumption of diets high in fat actually promotes short-term overconsumption of highly palatable foods (high in dietary fat).
The exact mechanisms by which maintenance of a HF diet leads to a reduction in sensitivity to satiation signals such as CCK and nutrients are not known. However, chronic HF feeding selectively reduces vagal and enteric neuronal sensitivity to intestinal oleic acid or CCK injection (40). Because fat is a potent stimulus for CCK release (12), it may be that modifications at the level of CCK-1 receptors play an important physiologic role. This is supported by evidence that continuous CCK infusion leads to downregulation of the receptor gene expression in rat pancreatic acinar cells (41) as well as in the central branch of the rat hypothalamo-pituitary-adrenal axis (42). However, Broberger and colleagues (43), using in situ hybridization techniques, reported that feeding a HF diet does not appear to alter vagal CCK-1 receptor mRNA expression. It remains to be determined whether alterations in CCK-1 receptors in other tissues accompany the diminished sensitivity of endogenous satiety mechanisms resulting from chronic consumption of dietary fat.
Dietary fat possesses a number of characteristics that may contribute to its overconsumption. Both palatability (44) and energy density (45,46) were shown to contribute to fat hyperphagia. In addition, fat was shown to be less satiating relative to carbohydrate or protein in both rats (3,47) and humans (48,49). More recently, it has become evident that fats may also contribute to hyperphagia through positive postingestive effects that can increase food preferences and acceptance. For example, using a self-regulated intragastric feeding 2-bottle test procedure, Lucas and colleagues (34) demonstrated that rats developed a preference for a flavor paired with a HF-diet infusion over a flavor paired with a LF-diet infusion. Although the preference test used in Expt. 2 did not reveal any significant differences for HHF food between LF- and HF-maintained rats, it is possible that our test was not sensitive enough to discriminate slight differences such as those employing liquid diets (34). Nevertheless, Expt. 1 revealed that rats fed the HF diet consumed greater amounts of the HHF diet, compared with LF-fed rats, and this cannot be attributed solely to potentially minute differences in increased preference.
Overconsumption of diets high in fat and energy density often leads to obesity in both rats (1,26) and humans (48,50,51). In our experiments, however, rats fed the HF diet did not gain more weight than rats fed an isoenergetic LF diet. These results are consistent with our previous data as well as those of others (52) indicating that consumption of HF diets does not invariably lead to weight gain when the energy density of the diets is comparable. Although HF-maintained rats in our study consumed the most energy derived from the HHF test meal, these rats also compensated the most by consuming a reduced amount of their maintenance diet. Accordingly, body weight gain was comparable between HF/HHF and LF/HHF rats, suggesting that daily consumption of a HHF food promotes weight gain irrespective of the habitual diet consumed. It is still reasonable to consider, however, that diminished satiation signaling accompanying HF diet consumption could contribute to overconsumption and the development of obesity in humans. In fact, there is evidence suggesting that obese individuals are prone to passive overconsumption when consuming a HF meal, whereas lean individuals appear to be more resistant to such a phenomenon (2). Satiation, which partly determines meal size, depends more on the preabsorptive effects of food, whereas postprandial satiety, which partly determines the delay between meals, is dependent on both the pre- and postabsorptive effects of food (53). Therefore, it is possible that the effect of adaptation to a HF diet on satiation is different, although not mutually exclusive from its effect on postprandial satiety. That is, although HF adaptation promotes short-term overconsumption of a high-energy food (i.e., diminished satiation), HF adaptation also appears to provide an important influence in the control of energy metabolism (54). Further, it is clear that long-term regulation of body weight results from a complex integration of hormonal, metabolic, and neural signals (55). One example of this interaction is the enhancement of responsiveness to the fat-cell hormone leptin by CCK. Specifically, Matson and colleagues (56,57) demonstrated that body weight loss after central leptin injections is amplified several fold by systemic CCK injections, without an accompanying synergistic reduction of food intake. These observations suggest that CCK released by a HF food might amplify leptin’s negative feedback control of body weight in rats fed a HF diet. Future studies exploiting HHF hyperphagia after chronic exposure to diets rich in fats and the potential development of obesity are warranted.
In conclusion, our study determined that rats fed diets high in fat are less sensitive to the satiating properties of a HHF food, and thus consume more food, compared with LF-maintained rats. This hyperphagia occurred even though all rats exhibited an equal relative preference for HHF food. Furthermore, HF-maintained rats in this study also demonstrated reduced sensitivity to exogenous administration of CCK compared with rats fed LF diets. Our results suggest that long-term HF diet consumption may promote excessive short-term energy intake by reducing sensitivity to at least 1 important feedback signal, which would ordinarily limit ingestion.
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FOOTNOTES |
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3 Abbreviations used: apo A-IV, apolipoprotein A-IV; CCK, cholecystokinin; HHF, high-energy, high-fat; HF, high-fat; HP, high-protein; LF, low-fat; OLETF, Otsuka Long Evans Tokushima fatty; rmANOVA, repeated measures ANOVA.
Manuscript received 18 March 2005. Initial review completed 8 April 2005. Revision accepted 17 May 2005.
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LITERATURE CITED |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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