Variety in the diet enhances intake in a meal and contributes to the development of obesity in the rat

Male and female rats were given three palatable, high energy foods either simultaneously or in succession during three 40 min courses. Both simultaneous and successive variety enhanced energy intake compared to the intake of single palatable foods, which was itself enhanced compared to the intake of chow. Rats deprived of food for 24 hr showed a compensatory increase in chow intake (84%) but only a 20% increase in intake in the single palatable food conditions, and no increase in the variety conditions. Male and female rats showed a similar response to variety and deprivation. The effect of variety on body weight was also examined in rats offered either chow, or chow and one palatable food, or chow and three palatable foods in succession (changed every 12 hr) or simultaneously, for seven weeks. All rats offered the palatable foods were hyperphagic compared to chow-fed controls. Rats given the simultaneous but not the successive variety diet were more hyperphagic than the other palatable food groups and showed significantly greater body weight and fat gains. The availability of a variety of foods is an important factor in the amount eaten in the meal and in the etiology of obesity.     

Individual effects of estradiol and progesterone on food intake and body weight in ovariectomized binge rats

The individual roles of estradiol (E) and progesterone (P) in the control of food intake and body weight in ovariectomized (OVX) rats were investigated. Six groups of OVX Sprague-Dawley rats (n = 9/group) were assigned to one of three 4-day cyclic hormone treatments: two groups were treated with E benzoate; two groups were treated with P; two groups were treated with both (EP). All rats had continuous access to chow and water throughout this 4-week study. One group of rats within each hormone treatment condition was fed chow ad libitum, and the second was subjected to a binge schedule: chow ad libitum plus 1-h access to an optional fat source on Monday, Wednesday, and Friday. A seventh OVX group (n = 8) received the oil vehicle and chow. This group was included to monitor body weight and to verify hormone efficacy. The main findings were: (1) relative to rats receiving only P, E alone or EP attenuated 24-h chow intake tonically and cyclically, i.e. intake on Day 4, which models estrus, was lower in E and EP than in P, and also was lower than intake on Day 2, which models diestrus. In contrast, (2) neither E nor EP detectably affected optional fat intake during the 1-h fat access period relative to rats receiving only P when data were collapsed across the entire study. However, (3) E and EP had large effects on fat intake relative to P during the 1-h fat access period at the start of the study, but not at the end, when bingeing was fully established. (4) E and EP led to lower and apparently normal levels of body weight compared to rats receiving only the oil vehicle or only P. These results indicate that (1) administration of E alone has similar effects as co-administration of E and P on feeding and body weight in rats bingeing on fat, (2) with or without P, the inhibitory effects of E on meal size are compromised when bingeing on fat, and (3) the effects of E on binge size change dynamically as bingeing develops.     

Effect of surfactant poloxalene 2930 on food intake, lipid absorption, and serum cholesterol in rats

Effect of hydrophobic surfactant, poloxalene 2930, on lipid absorption was studied in rats. Under acute conditions with surfactant infused intraduodenally with a lipid meal absorbed lipid accumulated abnormally in the enterocytes. This effect was quickly reversed after terminating treatment. Long-term administration of poloxalene given in semipurified diets resulted in changes in food intake, weight gain, fecal fat output, and serum cholesterol concentrations. The composition of the diet used as the vehicle for administration had a considerable effect on these results. When semipurified diets were used, food intake and weight gain were greatest when the dietary fat content was at the highest level. When the surfactant was given in ground chow, food intake was not affected and weight gain was only slightly, but significantly, less than the controls as a result of mild fat malabsorption. It is concluded that poloxalene 2930 affects lipid absorption, food intake, and serum cholesterol concentration but that results of this treatment are considerably affected by dietary factors.     

Lack of diet-induced thermogenesis in brown adipose tissue of obese medial hypothalamic-lesioned rats

Radiofrequency heat lesions were made in the medial hypothalamus of 12-week old male and female Holtzman rats. Two to three days later rats were offered a palatable cafeteria diet in addition to chow or were fed chow alone for the next 3-4 weeks. Male lesioned rats were only slightly hyperphagic on the chow diet and gained little extra weight. When fed the cafeteria diet, energy intake of male lesioned rats almost doubled in comparison with chow-fed lesioned rats and a very rapid extra weight gain occurred. Despite the marked hyperphagia, thermogenesis in brown adipose tissue was suppressed in the cafeteria-fed lesioned rats, as indicated by low mitochondrial guanosine diphosphate (GDP) binding. In female rats, lesions induced much greater hyperphagia and body weight gain than in male rats, particularly when they ate the cafeteria diet. Again, thermogenesis in brown adipose tissue was suppressed in the cafeteria-fed female lesioned rats. The proportion of energy derived from carbohydrate was not altered by the cafeteria diet in either male or female rats, whether lesioned or not, but there was an increase in the proportion of energy derived from fat at the expense of protein. No sex differences in food selection were observed. The accumulation of body fat was always greater in female lesioned rats than in male lesioned rats for similar food intakes. It is concluded that medial hypothalamic lesions prevent the normal occurrence of diet-induced thermogenesis in brown adipose tissue despite extreme overeating by the rats of a palatable cafeteria diet.     

Dietary fat-induced hyperphagia in rats as a function of fat type and physical form

The influence of dietary fat on food intake and weight gain was assessed by feeding adult female rats diets that differed in the type and form of fat, as well as in the availability of other macro- and micronutrients. Compared to chow-fed controls, the various fat diets increased total food intake by 4% to 27%. Specifically, rats fed chow and a separate source of fat (fat option diet) consumed more fat and total calories, and gained more weight when the fat source was emulsified corn oil rather than pure corn oil or was vegetable shortening rather than corn oil. However, corn oil and shortening had similar effects on caloric intake and weight gain when presented as emulsified gels. Also, pure and emulsified-gel forms of shortening did not differ in their effects on caloric intake and weight gain. Supplementing the vegetable shortening with micronutrients, however, enhanced its hyperphagia-promoting effect. The results of two-choice tests revealed that the rats' preferences for the orosensory properties of the various fat sources did not account for the differential hyperphagias obtained. Rather, it appears that long-term fat selection and caloric intake are influenced primarily by postingestive factors. Fat selection and total intake were determined not only by the fat source itself, but also by the other diet options. That is, rats selected more fat and consumed more calories when chow was the alternative food than when separate sources of carbohydrate and protein were available.     

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.     

Cyclic estradiol treatment normalizes body weight and test meal size in ovariectomized rats.

We tested whether cyclic estradiol treatment, like continuous estradiol treatment, is sufficient to normalize meal size and body weight in ovariectomized rats. In Experiment 1, adult Long-Evans rats were ovariectomized and subcutaneously injected with 0, 0.2, or 2.0 microg estradiol benzoate (EB) in sesame oil each Tuesday and Wednesday. Oil-treated ovariectomized rats gained more weight during 4 weeks of ad lib feeding (48 +/- 5 g) than intact rats (16 +/- 1 g, p < 0.01). Cyclic treatment with 2.0 microg EB normalized weight gain (11 +/- 2 g). During the next week, plasma samples were assayed for estradiol. Cyclic treatment with 2.0 microg EB produced excursions of plasma estradiol that appeared similar to those of intact, cycling rats: estradiol level reached 190 +/- 60 pmol/L after the second EB injection before decreasing to undetectable levels (<30 pmol/L) by cycle end. In Experiment 2, test meal sizes after overnight food deprivation were measured. Cyclic treatment with 2.0 microg EB produced both tonic (i.e., at cycle onset, meal size was smaller in estradiol-treated than oil-treated rats) and phasic (i.e., meal size was smaller late in the EB-treatment cycle than early in it) decreases in meal size. Thus, a weekly cyclic regimen of estradiol treatment that produces changes in plasma estradiol concentration similar to those in intact cycling rats is sufficient to produce the body weight and meal size patterns that characterize normal hypothalamic-pituitary-gonadal function.     

Ovarian influences on the meal patterns of female rats.

A series of experiments examined the effects of estrous cycles, ovariectomy, and estradiol-replacement on free-feeding meal patterns of female rats maintained on a liquid diet. The proestrous decrease in food intake was accomplished by a decrease in meal size and a less than fully compensatory increase in meal frequency. The hyperphagia induced by ovariectomy was reflected in an increase in meal size and a decrease in meal frequency. When food intake returned to preoperative levels, meal size remained elevated while frequency decreased further. Estradiol benzoate (2 μg/day) permanently decreased meal size in long-term ovariectomized rats. The subsequent return to food intake levels of controls was due primarily to an increase in meal frequency. These results suggest that the transient changes in food intake caused by estradiol withdrawal and replacement are accomplished by permanent changes in meal size followed by compensatory changes in the number of meals consumed per day. They suggest that the decrease in meal size at proestrus is due to a direct effect of estradiol on the mechanisms that terminate short-term food intake and are not secondary to changes in the level of total daily food intake.     

The effects of estradiol on body weight and food intake in normal weight VMH-lesioned rats.

The effects of estradiol on food intake and body weight were examined in ovariectomized and VMH-lesioned, ovariectomized rats that were prevented from supranormal weight gain by food restriction. Estradiol injections that were effective in reducing weight in supranormal weight, ovariectomized rats had no effect on weight in normal weight, ovariectomized or VMH-lesioned, ovariectomized rats. Estradiol did not prevent hyperphagia and weight gain in VMH-lesioned, ovariectomized rats when they were provided with ad lib food.     

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.     

Independent effects of diet palatability and fat content on bout size and daily intake in rats

Although considerable evidence attests to the hyperphagic effects of high-fat (HF) diets, the attribute(s) of these diets (e.g., palatability, caloric density, and postingestive effects) which promote overeating is still unclear. The present studies investigated the independent effects of diet palatability and macronutrient composition on intake using the self-regulated intragastric infusion paradigm. In Experiment 1, rats were infused with either HF or high-carbohydrate (HC) diet while drinking either saccharin (Sacc) or a more palatable saccharin-glucose (SaccGlu) test solution for 9 days. HF elicited greater daily intake than HC; lick pattern analysis revealed that HF produced larger but not more frequent bouts. Test solution was not related to intake, possibly due to the relatively modest palatability manipulation. Experiment 2 provided a more sensitive test: The palatability manipulation was strengthened and diet infusion made optional by provision of chow. HF again elicited larger bout size and total daily intake (diet+chow) than HC. Rats given the more palatable solution significantly increased intake (via larger bouts) and thus the amount of diet infused, but chow intake decreased such that total kilocalorie intake was not significantly related to solution palatability. The reliable observation that HF promoted larger bout size and greater total kilocalorie intake than HC provides additional evidence that fat sends weaker feedback signals relevant to controls of both satiation (suppression of ongoing eating, behaviorally manifest in meal size) and satiety (suppression of subsequent intake, reflected in total daily intake).     

Effect of food deprivation and maintenance diet composition on fat preference and acceptance in rats

High-fat diets typically elicit greater kcal intake and/or weight gain than low-fat diets. Palatability, caloric density, and the unique postingestive effects of fat have each been shown to contribute to high-fat diet hyperphagia. Because long-term intake reflects the sum of many individual eating episodes (meals), it is important to investigate factors that may modulate fat intake at a meal. The present studies used high-fat (hi-fat) and high-carbohydrate (hi-carb) liquid diets (both 2.3 kcal/mL) to assess the effect of hunger level (0 versus 24-h food deprivation) and fat content of the maintenance diet (12 versus 48%) on fat preference (when a choice among foods is offered in a two-bottle test), and acceptance (only one food offered) in male rats. Preference for hi-fat relative to hi-carb (two-bottle test) was enhanced by 24-h food deprivation, and by a high-fat maintenance diet. In contrast, neither deprivation nor maintenance diet composition influenced relative meal size (one-bottle test) of hi-fat and hi-carb: irrespective of test conditions, meal size of hi-fat was bigger than meal size of hi-carb.     

Central melanocortin receptor agonist reduces spontaneous and scheduled meal size but does not augment duodenal preload-induced feeding inhibition

Central melanocortin (MC) receptor agonists inhibit food intake and may be downstream mediators of the effects of central leptin, which (1) reduces food intake by selectively decreasing meal size and (2) augments the feeding-inhibitory effects of gastrointestinal food stimuli. Central administration of the MC-3/4 receptor (MC-3/4R) agonist, MTII, inhibits feeding in rats, but its effects on meal pattern and potential interactions with gastrointestinal controls of food intake remain unclear. We examined meal patterns and intake in male Sprague-Dawley rats following central intracerebroventricular administration of MTII (0.01-1.0 nmol) in two situations: (1) during daytime 60-min scheduled access to liquid glucose (12.5%) in combination with a duodenal preload of 12.5% glucose or physiological saline (4.4 ml/10 min), and (2) during subsequent overnight access to 45 mg of solid chow pellets. Both duodenal glucose preloads and MTII reduced subsequent glucose intake. However, no dose of MTII augmented the reductions in food intake produced by duodenal glucose alone. During overnight access to pelleted chow, the 0.1- and 1.0-nmol doses of MTII reduced food intake, meal size, meal duration, and body weight, and increased the satiety ratio (duration of intermeal interval/preceding meal size) but did not change meal frequency. The present data (1) demonstrate that MTII, like leptin, reduces food intake by a selective reduction in meal size and not meal frequency, and (2) suggest that MTII increases the feeding-inhibitory potency of negative feedback signals critical to the control of meal size during spontaneous chow access, but not scheduled access to palatable liquid nutrient solutions.     

Variation of fat intake with estrous cycle, ovariectomy and estradiol replacement in hamsters (Mesocricetus auratus) eating a fractionated diet

Intakes of fats, proteins, and carbohydrates were measured daily for a 3 month period in female hamsters maintained on a fractionated diet consisting of the dietary constituents, dextrose, fat and soybean meal. In the first study, hamsters showed variations in body weight and fat intake across the estrous cycle and following ovariectomy, with elevations during diestrous and after ovariectomy when endogenous estrogens are reduced. In the second study, the effects of exogenous estradiol or cholesterol on intake patterns of ovariectomized hamsters were determined. Hamsters lost weight and decreased fat intake when implanted with a silastic containing estradiol and gained weight and increased fat intake when exposed to cholesterol treatment. In neither of the two studies were the intakes of protein or carbohydrates significantly affected by the animals' hormonal status. These results suggest that in the hamster, estrogenic effects on food intake are specific to some dietary constituents and not to others.     

Estradiol decreases the orexigenic effect of melanin-concentrating hormone in ovariectomized rats

Estradiol exerts an inhibitory effect on food intake via interactions with anorexigenic peptides, like cholecystokinin, that function to decrease meal size. It is currently unknown whether estradiol also interacts with orexigenic compounds implicated in the physiological control of food intake. Thus, the primary goal of this study was to determine whether estradiol decreases the orexigenic effect of melanin-concentrating hormone (MCH), a neuropeptide that, like estradiol, appears to influence food intake by selectively affecting the controls of meal size. Food and water intake were monitored following lateral ventricular (icv) infusions of 5 mug MCH or saline vehicle in oil- and estradiol-treated ovariectomized rats. MCH increased food intake throughout the first 4 h of the dark phase in oil-treated rats, but only for the last 2 h of the same 4-h interval in estradiol-treated rats. As a result, the orexigenic effect of MCH was significantly lower in estradiol-treated rats, relative to oil-treated rats. During this interval of MCH-stimulated feeding, a prandial increase in water intake was not observed in either oil- or estradiol-treated rats. We conclude that estradiol decreases the orexigenic effect of MCH in ovariectomized rats.     

Palatable daily meals entrain anticipatory activity rhythms in free-feeding rats: dependence on meal size and nutrient content

Circadian wheel-running rhythms were monitored continuously in 3 groups of female Sprague-Dawley rats under different palatable food availability schedules. All rats had free access to standard rat chow and water throughout the study. In addition, Group 1 rats received a palatable nutrient-rich mash for 2 hr each day for 28 days, beginning 3 hr after light onset of a 12:12 LD cycle. Group 2 rats received the same mash but were limited to 4 g daily. Group 3 rats received a palatable non-nutritive mash. Ten of 13 Group 1 rats, 2 of 13 Group 2 rats, and 0 of 13 Group 3 rats showed anticipatory running prior to the daily palatable meal. Palatable mash intake was generally lower among Group 3 rats than among Group 1 rats. However, several Group 3 rats consumed non-nutritive mash in amounts which equalled or exceeded the nutritive mash intake of Group 1 rats showing anticipatory running. The results indicate that temporally limited daily access to a palatable food can entrain anticipatory wheel-running in rats that are not food-deprived. They also indicate that entrainment to periodic food availability depends on stimuli associated with the concentrated intake of nutrients rather than on the absolute size or palatability of a meal.     

Lack of diet-induced thermogenesis following lesions of paraventricular nucleus in rats

The effects of electrolytic lesions in the hypothalamus paraventricular nucleus were studied in adult male and female Sprague-Dawley rats, fed different diets, consisting of either palatable human food plus chow (cafeteria diet) or chow alone. The results showed that both cafeteria diet and lesions induced an increase in energy intake and weight gain in rats of both sexes. Oxygen consumption rate and colonic temperature were significantly decreased by lesions, while cafeteria diet increased the same parameters only in intact animals. The lesion decreased weight, protein and DNA, and temperature of brown adipose tissue, while cafeteria diet increased the values considered in brown adipose tissue of sham-injured rats, but not in lesioned animals. The response to norepinephrine administration was significantly greater in intact rats and those fed cafeteria diet. The results suggest that the larger body weight gain observed in lesioned rats, particularly evident in rats fed cafeteria diet, is partly due to the disappearance of diet-induced thermogenesis that depends on the reduced mass and functional activity of brown adipose tissue.     

Effects of abuse pattern of gestational toluene exposure on metabolism, feeding and body composition

AIMS: Inhalant abuse during pregnancy lowers birth weight and impedes early development. These studies explored the effects of brief, repeated, prenatal toluene exposures in pregnant female rats on body weight, metabolic rate, body composition, and food intake in their offspring. METHOD: Rats were exposed to 0, 8000, 12,000, or 16,000 ppm of toluene twice daily for 15 min from gestational days 8 to 20. The effects of such exposures on post-weaning litter weights, oxygen consumption, carbon dioxide output, and body fat content were determined in 2 cohorts (n=23, n=24) of offspring. Food intakes and weight changes in response to 3 different diets (regular chow, purified diet, purified high fat diet) were examined in another cohort (n=24) from postnatal days 72 to 116. RESULTS: Litter weights showed a significant linear decrease as a function of toluene dose. Offspring exposed to the 16,000 ppm toluene dose displayed statistically lower energy expenditures than control rats. Male rats exposed to 8000 or 16,000 ppm toluene had significantly greater percentage of body fat as well as total body fat than the other groups. Toluene also significantly suppressed weight gain over the time chow was consumed compared to the 0 ppm control group. Finally there were trends for a main effect of toluene dose on food intake during chow and during high fat diet consumption, with rats in the 12,000 ppm group consuming more than the 0 ppm group on both diets. DISCUSSION: These data suggest that, in addition to other previously documented abnormalities in neurological development and behavior, the physiological regulation of metabolism and body composition in males as well as food intake and weight gain in both sexes may be altered by prenatal exposure to toluene.     

Acute exposure to a high-fat diet alters meal patterns and body composition

Weight gain and adiposity are often attributed to the overconsumption of unbalanced, high-fat diets however, the pattern of consumption can also contribute to associated body weight and compositional changes. The present study explored the rapid alterations in meal patterns of normal-weight rats given continuous access to high-fat diet and examined body weight and composition changes compared to chow fed controls. Ten Long-Evans rats were implanted with subcutaneous microchips for meal pattern analysis. Animals were body weight matched and separated into two groups: high-fat or chow fed. Each group was maintained on their assigned diet for nine days and monitored for 22 h each day for meal pattern behavior. Body weight was evaluated every other day, and body composition measures were taken prior and following diet exposure. High-fat fed animals gained more weight and adipose tissue than chow fed controls and displayed a reduced meal frequency and increased meal size. Furthermore, meal size was significantly correlated with the gain of adipose tissue. Together, these results suggest that consumption of a high-fat diet can rapidly alter meal patterns, which in turn contribute to the development of adiposity.     

Exercise and the development and persistence of dietary obesity in male and female rats

Adult male and female hooded rats were housed in sedentary conditions or were given free access to a running wheel. Exercising and sedentary rats received either a palatable, mixed, high energy diet with chow (experimental group) or only chow (control group). Exercise reduced the weight gain of the males but not of the females. All experimental groups preferentially selected the palatable foods. Both exercising and sedentary females and the sedentary males became obese compared to their controls, but the exercising males did not. The mixed diet was withdrawn after 10 weeks: thereafter the male and female sedentary experimental groups maintained the elevated body weight. The exercising experimental females showed significant weight loss. Analysis of x-ray photographs indicated that elevated body weight in the experimental rats probably reflected increased deposition of fat and not skeletal growth. The results show that the effect of exercise on the development of dietary obesity is different in males and females, and that sedentary male and female rats can both show persistent dietary obesity after withdrawal of the palatable foods.