Effects of dietary caloric density on feeding behavior in Mongolian gerbils (Meriones unguiculatus)

Total daily energy intake, water intake, body weight, and meal patterns were studied in Mongolian gerbils as a function of dietary caloric density. On diets ranging in caloric density from 2.25 kcal/g to 6.09 kcal/g, gerbils consumed an average of 40 kcal per 100 g of body weight per day. In comparison to gerbils fed ground Purina Laboratory Chow (4.2 kcal/g), gerbils presented with diets diluted with nonutritive cellulose increased food intake in proportion to the percentage of cellulose added. Gerbils given diets in which the caloric density was increased by the addition of fat, decreased food intake as a direct function of the added fat. Water intake was increased on the calorically diluted diets, and decreased on the concentrated diets. Body weight did not vary as a function of dietary conditions. On a standard pelleted diet (Noyes), gerbils ate approximately 18 meals a day. Average meal size was 0.4 g. When presented with calorically diluted pellets, gerbils maintained daily energy intake by increasing both meal frequency and meal size. There were no differences in food intake, meal frequency or meal size between the light and dark portions of the 24-hr cycle.     

Consumption of a high-fat diet alters the homeostatic regulation of energy balance

Humans in many countries are currently experiencing what has been called an epidemic of obesity. That is, the average body weight (and amount of fat stored in the body) is increasing over years, carrying with it a multitude of associated medical, psychological, and economic problems. While there is no shortage of possible causes of this epidemic, increased availability and consumption of high-fat (HF), calorically dense and generally quite palatable food is often touted as a likely culprit. In order to better assess the impact of consuming a diet with those qualities, we have developed a well-controlled animal model in which the effects of chronic consumption of a high-fat diet can be dissociated from those of becoming obese per se. Long-Evans rats are fed one of two semipurified pelleted diets, a HF diet that contains 20% fat by weight and a low-fat (LF) diet that contains 4% fat by weight. Pair-fed animals consume the HF diet but are limited to the daily caloric intake of LF rats. Another group receives pelleted chow. Relative to animals consuming diets low in fat, HF animals weigh more, have more carcass fat, are hyperinsulinemic and hyperleptinemic, and are insulin resistant. HF-fed animals, independent of whether they become obese or not, also have central insulin and MTII insensitivity. Finally, HF rats have a down-regulated hypothalamic apo A-IV system that could contribute to their hyperphagia.     

Liquid diet preference in weanling rats with dorsomedial hypothalamic lesions

Two groups of weanling rats received bilateral electrolytic lesions in the ventromedial and dorsomedial hypothalamic nuclei, respectively. Sham-operated animals served as controls. During 14 days post-operation, the intake of standard laboratory chow was measured. The rats then received, in addition to laboratory chow and tap water, a sweet, eggnog-type liquid diet for 17 days, during 14 of which food intake from both diets was measured daily. The liquid diet was then withdrawn and for two weeks laboratory chow was again the sole source of calories. During the availability of the liquid diet, both groups of rats with hypothalamic lesions profoundly reduced their intake of laboratory chow but conspicuously increased their consumption of liquid diet. The rats with dorsomedial lesions consumed as much liquid diet as the controls, while on laboratory chow alone they were highly significantly hypophagic compared with the controls. During the availability of the liquid diet the rats with dorsomedial lesions also became obese, but after the return to a period in which laboratory chow was the sole source of calories they lost this extra fat while again being hypophagic.It is suggested that the hypophagia observed in rats lesioned in the dorsomedial hypothalamic nucleus is not due to a deficiency in caloric metering but rather, alternatively, to (a) aversion to dry food, (b) taste preference for a sweet, liquid diet, (c) a motivational deficit or (d) a motor deficit.     

Facilitation of hypothalamic obesity by greasy diets: Palatability vs lipid content

Rats with obesifying lesions of the ventromedial hypothalamus (VMH), obesifying hypothalamic knife cuts, or sham operations, were given a synthetic powdered high-fat diet and/or an isocaloric and preoperatively preferred synthetic powdered control diet. Postoperatively the knife-cut rats preferred, overate, and became obese on the high fat diet. The electrolytically lesioned rats did not show a switch in preference, but they did overeat and became obese on the synthetic high fat diet when it was the only diet available. Thus, postingestive aspects of high-fat diets contribute to overeating. When a standard Purina chow diet was subsequently presented as pellets instead of as powder, overeating again occurred. In this case preingestive factors alone facilitated feeding. When firm consistency, high fat content, and high caloric density were combined in a Purina/Crisco high fat diet, the greatest intakes and weight gains of all three tested diets were obtained. Thus, both pre- and postingestive changes in response to the diet appear to contribute to the mediation of hypothalamic obesity. These factors not only persist, but are exaggerated in the obesity elicited by hypothalamic knife cuts.     

Diet composition alters the satiety effect of cholecystokinin in lean and obese Zucker rats

Although exogenous administration of the peptide cholecystokinin (CCK) has been shown to reduce food intake in a variety of experimental situations, few studies have examined the influence of dietary content upon CCK's effectiveness, particularly in obese states. To evaluate the effectiveness of CCK administration in animals consuming high fat diets, groups of obese and lean Zucker rats were maintained on laboratory chow (CH), a high fat diet isocaloric to chow (IF), or a hypercaloric fat diet (HF). After a 17 hr fast, rats were given intraperitoneal injections of saline or ascending doses of 0.06 to 2.0 micrograms/kg of the synthetic octapeptide of CCK. On all diets, obese rats required higher doses of CCK to significantly reduce feeding and showed smaller intake reductions than lean rats (p less than 0.001). Despite higher baseline caloric intakes (p less than 0.001), rats of both genotypes maintained on HF displayed larger reductions of intake than those fed IF or CH (p less than 0.001). Intake reductions by either genotype maintained on IF or CH were not reliably different. The manner in which the satiety effect of CCK was enhanced in rats consuming the calorically dense, palatable HF diet is unclear but may be related to orosensory and/or postingestive attributes of the diet.     

Responses to protein dilution in the adult female rat

Adult female rats were given ad lib access to 3 food cups containing casein, cornstarch, and a fat mixture, or a composite diet formulated from these nutrients. One-half of the animals in each diet condition were subjected to 25, 50, 150, and 500% sequential dilutions of the casein or the composite diet. Self-selecting rats decreased intake of the diluted casein, but increased consumption of cornstarch, so that total caloric intake remained constant. Composite-fed rats compensated for dilution by increasing the volume of diet consumed, but caloric regulation was less precise than in self-selectors.     

Area postrema/nucleus of the solitary tract ablations: Analysis of the effects of hypophagia

The effect of hypophagia following lesions of the area postrema and caudal-medial aspect of the nucleus of the solitary tract (AP/cmNTS) on body-weight, water intake and preference for palatable diets was examined. Following AP/cmNTS ablation, rats reduced pelleted-food intake to a degree which was sufficient to account for the weight loss and increased water:food ratios observed. Restricting food intakes of intact rats to levels taken by lesioned animals resulted in similar weight losses and increased water:food ratios. When offered both pelleted food and milk, lesioned rats took more calories as milk than did previously food-restricted intact rats. Thus, the hypophagia of AP/cmNTS lesioned rats does not account for their increased preference for milk diets. Lesioned rats ate less high-fat diet than did intact or sham-lesioned controls and did not increase their intakes when this diet was sweetened. At autopsy, retroperitoneal and epididymal fat-pad weights accounted for less of the total body weight of lesioned animals than controls suggesting that body-fat levels are reduced following AP/cmNTS ablation.     

Consumption of a high-fat diet induces central insulin resistance independent of adiposity

Plasma insulin enters the CNS where it interacts with insulin receptors in areas that are related to energy homeostasis and elicits a decrease of food intake and body weight. Here, we demonstrate that consumption of a high-fat (HF) diet impairs the central actions of insulin. Male Long-Evans rats were given chronic (70-day) or acute (3-day) ad libitum access to HF, low-fat (LF), or chow diets. Insulin administered into the 3rd-cerebral ventricle (i3vt) decreased food intake and body weight of LF and chow rats but had no effect on HF rats in either the chronic or the acute experiment. Rats chronically pair-fed the HF diet to match the caloric intake of LF rats, and with body weights and adiposity levels comparable to those of LF rats, were also unresponsive to i3vt insulin when returned to ad libitum food whereas rats pair-fed the LF diet had reduced food intake and body weight when administered i3vt insulin. Insulin's inability to reduce food intake in the presence of the high-fat diet was associated with a reduced ability of insulin to activate its signaling cascade, as measured by pAKT. Finally, i3vt administration of insulin increased hypothalamic expression of POMC mRNA in the LF- but not the HF-fed rats. We conclude that consumption of a HF diet leads to central insulin resistance following short exposure to the diet, and as demonstrated by reductions in insulin signaling and insulin-induced hypothalamic expression of POMC mRNA.     

Preference of rats for food flavors and texture in nutritionally controlled semi-purified diets

Preference for nutritionally controlled, semi-purified diets modified by the addition of potent food flavors was determined for Sprague Dawley rats using two-choice diet preference tests. Intake of each food cup was monitored after 1 hr and for each 24 hr period thereafter up to 5 days. Preference was also determined for the flavored diets prepared in three forms differing in texture: powdered, and pellets of two sizes. Rats easily detected minor amounts of the food flavors, and the tests provided a catalog of 12 preferred flavors. Exposure time to the diets altered preference for a minority of flavors; diets initially avoided in the first hour test were likely to become less aversive upon continued exposure. Whether or not a specific flavored diet was preferred, total food intake was not affected during the 5 day period monitored. Rats displayed strong preference for diets of a pelleted texture compared to the same diets in a powdered form.     

Effect of liquid and solid preloads on eating behavior of obese and normal persons

Although the obese are unresponsive to internal state and generally regulate their caloric intake poorly, recent studies suggest that the nature of the food may be important. An experiment was conducted to test the regulation of obese and normal weight humans after liquid or solid preloads of 200 or 600 calories. Normal subjects regulate in accordance with caloric preload on both the liquid and solid diets. Obese subjects regulate intake on the liquid diet and not on the solid diet.     

Protein selection, food intake, and body composition in response to the amount of dietary protein

Though not universally observed, moderately low-protein diets have been found to increase caloric intake and body fat. It appears that animals overeat in calories in order to obtain more dietary protein. For animals to control protein intake, they must be able to distinguish between two isocaloric diets containing different percentages of protein and make the appropriate dietary selection on the basis of their previous history of protein intake. Experiment 1 examined the 24-h diet selection (5 vs. 35% casein) of Sprague-Dawley rats that had been previously fed diets containing various percentages of dietary protein (5, 10, 20, 35, or 60% casein). Animals fed 5, 10, or 20% dietary protein showed a preference for the higher protein selection diet. In contrast, no significant diet preference was found in animals pre-fed the two higher levels of dietary protein (35 or 60% casein). In this study, daily food intake and body fat of rats fed the low-protein diets (5 and 10% casein) were similar to rats fed the 20% casein diet. Experiment 2 examined the effects of the level of methionine supplementation on rats fed 10% casein. In this study, food intake and body fat were increased by approximately 20% in rats fed 10% casein diets, regardless of the level of methionine supplementation (0.3 vs. 0.15%). Together, the results suggest that the presence of low-protein-induced hyperphagia helps maintain body protein levels in the face of moderately low dietary protein and promotes an increase in the amount of body fat and energy.     

Somatic and metabolic responses of mature female rats with dietary obesity to dorsomedial hypothalamic lesions: Effects of diet palatability

Caloric intake, body weight, obesity status (Lee Index) and incorporation of U-14 C-glucose into liver and retroperitoneal fat pad glycogen and lipid were studied in mature female rats that had received bilateral lesions or sham-operations in the dorsomedial hypothalamic nuclei (DMN) after dietary obesity was well established. Their diet consisted of a high-fat-sucrose chow mix, chocolate chip cookies and a drinking fluid of 32% sucrose in tap water. Comparable groups of DMN lesioned rats (DMNL rats) and sham-operated controls were maintained on lab chow pellets and tap water. Prior to the hypothalamic operation, the animals on the high-caloric regimen consumed significantly more calories than the rats on lab chow and also attained commensurately higher body weights and obesity indices. The bulk of the calories consumed during this time was derived from the cookies. Following DMNL, the animals maintained on lab chow became hypophagic and had lower body weights than the sham-operated rats, as has been previously reported. In rats on the high-caloric regimen, DMNL resulted in hyperphagia in comparison to all other groups. The greatest percentage of the calories during this time was derived from the high-fat-sucrose chow mix and sugar water. Correspondingly, DMNL rats on the high-caloric regimen had higher body weights and obesity indices than all other groups. At sacrifice, both a diet and lesion effect were noted in an elevated incorporation of U 14-C glucose in both fat pad and liver lipid and glycogen. The data are interpreted to mean that (1) when a highly palatable, high-caloric diet is available, DMNL do not exert their usual hypophagic and weight-lowering effects; (2) DMNL and control rats show excessive caloric intake when both groups are fed a highly palatable, high-caloric diet in comparison to their chow-fed counterparts. However, DMNL rats fed high-caloric diet also consume significantly more than controls fed this diet; (3) This excessive caloric intake of the DMNL rats possibly predisposes these animals to exaggerated lipogenesis in liver and adipose tissue; (4) the sham-operated controls on the high-caloric regimen also show greater lipogenesis but at a level intermediate between the chow-fed controls and the DMNL rats on the high-caloric diet.     

Influence of early dietary experience on energy regulation in rats

The environmental mechanisms that have contributed to the rapid increases in overweight and obesity in the US over the past 25-30 years have yet to be fully specified. One hypothesis that has been forwarded is that increased consumption of calories in liquid form may be a contributing factor, since some studies support the idea that caloric compensation is less adequate for liquid calories compared to calories delivered in more solid form. Work from our laboratory using rats has examined the role that differences in diet viscosity may play in altering energy intake and body weight regulation. This work has suggested that when offered diets matched on caloric density, macronutrient and micronutrient composition, and differing only in viscosity, adult rats fail to compensate for calories delivered in low-viscosity form in short-term intake tests. Further, long-term consumption of low-viscosity diets leads to enhanced weight gain in adult rats. In the present studies, we examined whether short- or long-term exposure to varying relationships between viscosity and calories led to altered food intake or body weight regulation in juvenile rats. The results demonstrated that animals given either short- or long-term experience with direct relationships between viscosity and calories (high viscosity, high calorie meals and low viscosity, low calorie meals) did not differ in food intake or body weight gain compared to animals given short- or long-term experience with indirect relationships between viscosity and calories (high viscosity, low calorie meals and low viscosity, high calorie meals). When juvenile rats were given long-term (9 weeks) exposure to a single, high or low viscosity diet supplement, matched on caloric density and differing only in viscosity, there were no effects on body weight gain. However, analysis of body composition using DEXA demonstrated that animals consuming the low viscosity supplements had significantly greater body fat than animals that consumed either the high viscosity supplement or no dietary supplement at all. These differences in body fat persisted for at least 3 months following the cessation of dietary supplements; during this 3-month period, animals previously exposed to the low viscosity supplement also gained significantly more weight than animals previously exposed to the high viscosity supplement. Taken together, the results suggest that consuming calories in low viscosity form may contribute to poor intake regulation over the short-term and to increased adiposity over the long term. When animals experience these diets as juveniles, these effects may persist into adulthood.     

Effect of amygdaloid lesions on dietary intake of disproportionate amounts of amino acids

Male rats with bilateral electrolytic lesions in the anterior, medial or posterior aspects of the ventral amygdala and groups of intact rats were fed, in turn, basal, imbalanced or deficient amino acid diets involving threonine or isoleucine as the limiting amino acid, and then a low protein (6% casein) followed by a high protein (75% casein) diet. No change in food intake was observed in animals fed the threonine basal diet postoperatively. When the threonine or isoleucine imbalanced diet was substituted for the respective basal diet, animals with lesions in certain areas of the medial amygdala showed little or no depression in food intake of the imbalanced diets, while all other rats with amygdala lesions reduced their food intake markedly, as did intact controls, when fed such diets. All animals, however, curtailed their food intake of the deficient or high protein diets. The lack of responsiveness of the animals with medial amygdaloid lesions to the imbalanced diets suggests that these areas may be involved in a system regulating food intake of animals fed diets containing imbalanced amino acid mixtures.     

Selection of protein and fat by diabetic rats following separate dilution of the dietary sources

Diabetic and normal rats were allowed to select their diets from separate sources of protein, carbohydrate and fat. Following the determination of baseline intakes, diabetic and normal rats received dietary components in which either the protein (Experiment 1) or fat source (Experiment 2) was diluted by 25% or 50% by the addition of cellulose. Diabetic rats failed to maintain protein intake at both dilution levels, but made up for the loss of protein-derived calories by consuming more fat. Diabetic rats maintained fat intake at both dilution levels. Dietary dilutions had no effect on total caloric intakes or body weight gain of diabetic rats. Diabetic status, measured by fasting plasma glucose levels and urinary glucose excretion rates, also was unaffected by diet dilutions. These data suggest that diabetic rats maintain total caloric intake following dilution of either the protein or fat source of their diets, but defend intake of fat-derived calories more readily than protein-derived calories. Normal rats maintained both protein and fat intake at the 25% but not at the 50% dilution level. These findings are discussed in terms of the ability of diabetic rats to solve the metabolic problems associated with their diabetic condition.     

Effects of dietary dehydroepiandrosterone on food intake and body weight in rats with medial hypothalamic knife cuts

Dehydroepiandrosterone (DHEA) is a steroid which has been reported to have anti-obesity effects when added to the diets of rats and mice. In this report, rats made hyperphagic with medial hypothalamic knife cuts were placed on a diet containing 0.45% DHEA or a control diet. Knife cut rats on the control diet ate more food and gained more weight than sham-operated rats on the control diet. In contrast, knife cut rats fed the DHEA diet weighed the same as shams on the DHEA diet and were only observed to be hyperphagic on one of eight 24 hour measurements taken during a five week period. Dietary DHEA reduced food intake and body weight of both knife cut and sham-operated rats, though the effects were smaller in shams. As these effects of DHEA were reminiscent of the effects of dietary quinine adulteration on intake by knife cut rats, a second experiment measured the food intake of unoperated rats when given a choice between a control high-fat diet and one adulterated with various concentrations of DHEA. Even at a concentration of 0.05%, rats clearly identified and avoided the DHEA-adulterated diet. While these results do not rule out effects of DHEA on metabolic rate or lipogenesis, they do indicate that the unpalatability of DHEA-adulterated diets may be a contributing factor in the observed effects on food intake and body weight.     

Energetics of meal patterns in rats

Meal patterns in rats were examined as functions of the caloric density and availability of the diet. Three diets were used, a standard laboratory diet (3.6 kcal/g), a calorically diluted diet (2.7 kcal/g), and a calorically concentrated diet (4.5 kcal/g). After obtaining ad lib measures of meal patterns on each diet availability of food was constrained by requiring the rats to complete fixed ratio requirements of barpresses to obtain access to a meal. On all 3 diets, meal frequency decreased, while meal size and duration increased as functions of the ratio requirement. Under ad lib conditions and low ratio requirements, in comparison to the standard diet, meal frequency was greater on the diluted diet and less on the concentrated diet. Meal size did not vary as a function of diet on low ratio schedules. At high ratio requirements, rats continued to maintain caloric intake on the diluted diet by increasing meal frequency. On the concentrated diet, however, rats maintained intake at high ratio values by decreasing meal size rather than meal frequency. The results indicate that the rat can adopt a variety of strategies to solve the problem of controlling energy intake constant across the daily feeding cycle.     

Macronutrient selection through post-ingestive signals in sharpsnout seabream fed gelatine capsules and challenged with protein dilution

Sharpsnout seabream ability for macronutrient self-selection was studied using gelatine capsules containing pure macronutrients. In particular, the existence of non-oropharyngeal chemosensory pathways involved on protein (P), fat (F) and carbohydrate (CH) selection, as well as sharpsnout seabream response to dietary protein dilution were investigated. In a sequence of experimental phases, sharpsnout seabream were fed a pelleted complete diet, an encapsulated complete diet or a combination of separately encapsulated pure macronutrients. In order to induce associative learning, capsules containing a given macronutrient were paired with a particular colour. The animals composed a diet containing 62.7% P, 21.3% CH and 16.0% F, in terms of macronutrient percentage intake, and this selection pattern was maintained throughout all experimental phases. In a second experiment, individually kept sharpsnout seabream were challenged with protein dilution. After protein capsules were diluted (from 91.9% P to 56.3% P) with cellulose, the animals increased their protein intake to compensate for dilution in such a way that their energy intake was not significantly modified (17.4 kJ/100 g BW vs. 17.6 kJ/100 g BW after dilution). These results show that sharpsnout seabream feeding on encapsulated diets are able to select and maintain a particular diet composition, as well as sustain their energy intake, without using the diet's oropharyngeal chemosensory properties. Moreover, they were also able to maintain their protein intake after dilution, which highlights the importance of this macronutrient in this omnivorous species.     

Sham feeding is inhibited by dietary-induced obesity in rats

A group of six female, albino rats were maintained on a cafeteria diet of cookies, milk, and elevated-fat (shortening), rat-chow mixture and rat chow while a similar group received only rat chow ad lib for 17 weeks. When the groups differed significantly in mean body weight (obese-387.5 g, controls-287.2 g; p less than 0.001), gastric fistulas were implanted in each animal. After recovery, the rats were adapted to a liquid diet and assessed for sham feeding. Control-fed, normal-body-weight subjects showed substantial sham feeding when ingesting the Vivonex with the fistulas open compared to fistula-closed intake; meal frequency, meal size (apart from the initial meal) and total food intake were significantly increased while the satiety ratios following each meal were significantly decreased. Obese animals showed no significant increased feeding and satiety ratios were unreliably altered; while normal-body-weight controls increased 4-hr food intakes by 93% and halved their mean satiety ratios the obese animals showed an 8% increase in 4-hr food intake and only a 22% decrease in mean satiety ratios. We offer the hypothesis that, when animals are induced to become obese by palatable and varied diets which are then terminated, the anorexia produced is independent of gastrointestinal interactions inasmuch as that anorexia extends to sham feeding.     

Hepatic vagotomy disrupts somatotropin-induced protein selection

Rats treated with somatotropin (STH) and allowed to self-select between diets varying in protein content will consume more of the high-protein diet. The objective of this study was to determine the role of the hepatic vagus nerve in this ability to select protein. Female Sprague-Dawley rats (n=40) received a hepatic vagotomy (HVAGX) or a sham surgery. Postsurgery, the rats were maintained on pelleted diets for 2 weeks, after which the rats were adapted to selecting between powdered diets with 5% casein and 30% casein. After a 7-day adaptation to diet selection, rats in each surgical treatment group were treated with STH (4 mg/day) or physiological saline for 14 days. Body weight and intake were recorded daily. STH treatment increased growth rate to a similar degree in both sham and HVAGX groups. Despite causing an increase in total food intake, there was no effect of HVAGX alone on body weight. Relative to the sham-saline group, sham-STH in treated rats had greater total food intake that was accounted for entirely by increased consumption of the 30% protein diet and no change in intake of the 5% diet. In contrast, HVAGX+STH rats exhibited 20-30% increases in consumption of both the 5% and 30% protein diets. Thus, the HVAGX+STH rats recognized an increased need for protein, but were unable to distinguish between the high- and low-protein diets and selected more of both. The data suggest that the ability to alter diet selection in response to a stimulation of protein accretion is at least partially mediated through the liver and hepatic branch of the vagus nerve.