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.     

Sex differences in the effects of voluntary activity on sucrose-induced obesity

Sedentary, adult rats of both sexes fed Purina chow and a 32% sucrose solution overate, gained excess weight and had higher Lee Indexes of obesity than control animals fed only Purina chow. The magnitude of these effects was similar in the males and females. Animals of both sexes fed the sucrose diet showed a slower rate of weight loss during food deprivation than the chow controls. Access to an activity wheel led to a reduction in caloric intake and the elimination of obesity in male rats. In the chow fed male rats activity led to a smaller, transient suppression in caloric intake and a slightly lower level of body weight than the sedentary chow controls. Access to activity did not affect body weight in the female rats in either dietary condition. Rather, both active groups of female rats appeared to compensate for the energy cost of voluntary activity by a small increase in food consumption. Long-term exposure to activity was associated with more rapid weight loss during food deprivation in both males and females. These data reveal that high levels of activity and obesity can co-exist when normal female rats are fed a palatable diet but that activity eliminates this form of obesity in the male rat.     

Food selection during recovery from protein restriction in lactation.

Lactating rats were fed a 12% or 25% casein diet. After the pups were weaned on Day 21, dams were given ad lib access to three food cups containing protein, carbohydrate, and fat. Both groups were hyperphagic for three to four weeks. Previously, protein-restricted rats consumed more protein than controls during Weeks 2 and 3, but protein intake returned to control levels as body weight recovered.     

The weanling rat ventromedial syndrome: males get just as fat as females

Weanling female and male Holtzman rats received bilateral electroytic lesions in the ventromedial hypothalamic nucleus (VMN) at the age of 27 and 26 days, respectively. Sham-operated rats served as controls. The animals were maintained on a synthetic diet (4.2 Cal/g) and tap water ad lib, and body weight, Lee (obesity) Index, tail length and food and water intake were recorded weekly for 6 weeks. The only parameters in which a significant sex difference could be demonstrated were body weight gains and water intake which were greater in the male VMN rats. Female and male VMN rats also utilized food energy for fat deposition, body weight and body length change to the same extent. The data also show that in growing animals, body weight is a poor criterion for the accurate assessment of obesity status and true growth.     

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.     

Sucrose-induced hyperphagia and obesity in rats fed a macronutrient self-selection diet

Adult female rats were allowed to self-select their diet from separate sources of fat, protein, and carbohydrate (starch). Other rats were fed a composite diet that matched the nutrient composition chosen by the self-selecting rats (50% fat, 28% protein, 22% carbohydrate) or a low-fat, high-carbohydrate chow diet. Half of the rats in each diet condition were given access to a 32% sucrose solution for 30 days. Sucrose availability increased total caloric intake (approximately 20%) and body weight gain in all three groups compared to control groups not fed the sucrose solution. The selection animals compensated for their sucrose intake by reducing their fat intake, and to a lesser degree, their starch intake; protein intake was the least affected by sucrose availability. The selection rats consumed less sucrose than the chow-fed rats and displayed a smaller increase in weight, relative to controls, than the chow-fed rats. These differences were attributed to the high-fat intake of the selection animals since similar results were obtained with the rats fed the composite diet. In particular, both the selection and composite diets produced mild obesity in the absence of sucrose. The results demonstrate that sucrose-induced overeating and overweight is not an artifact of restraining the diet choices of rats to a pure sugar and a nutritionally complete diet.     

Dynamic body weight and body composition changes in response to subordination stress

Social stress is prevalent in many facets of modern society. Epidemiological data suggest that stress is linked to the development of overweight, obesity and metabolic disease. Although there are strong associations between the incidence of obesity with stress and elevated levels of hormones such as cortisol, there are limited animal models to allow investigation of the etiology of increased adiposity resulting from exposure to stress. Perhaps more importantly, an animal model that mirrors the consequences of stress in humans will provide a vehicle to develop rational clinical therapy to treat or prevent adverse outcomes from exposure to chronic social stress. In the visible burrow system (VBS) model of chronic social stress mixed gender colonies are housed for 2 week periods during which male rats of the colony quickly develop a dominance hierarchy. We found that social stress has significant effects on body weight and body composition such that subordinate rats progressively develop characteristics of obesity that occurs, in part, through neuroendocrine alterations and changes in food intake amount. Although subordinate rats are hyperphagic following social stress they do not increase their intake of sucrose solution as control and dominants do suggesting that they are anhedonic. Consumption of a high fat diet does not appear to affect development of a social hierarchy and appears to enhance the effect that chronic stress has on body composition. The visible burrow system (VBS) model of social stress may be a potential laboratory model for studying stress-associated metabolic disease, including the metabolic syndrome.     

Patterns of nutrient selection in rats with streptozotocin-induced diabetes

The effects of experimental diabetes on energy intake, patterns of nutrient selection, water intake, body weight and body composition were examined in male Sprague-Dawley rats given ground Purina Chow or a dietary self-selection regime. Following adaptation to dietary conditions, a portion of the animals in each diet group were made diabetic by the administration of 45 mg/kg streptozotocin (STZ). The remaining animals in each group served as vehicle-injected controls. STZ reliably produced diabetes in rats on both dietary regimes. Immediately after the induction of diabetes, rats on the self-selection regime increased carbohydrate and protein intakes and decreased fat intake. Approximately three weeks after STZ administration, diabetic rats reduced carbohydrate intake and increased fat intake. Diabetic animals in both diet groups were hyperphagic and polydipsic relative to non-diabetic controls. During the first three weeks following STZ injections, energy and water intakes of diabetic animals in the two dietary conditions were similar. However, after this initial period, energy and water intakes of diabetic rats given the self-selection regime were significantly lower than those of diabetic animals given Purina Chow.     

Pregnancy and lactation in the obese rat: Effects on maternal and pup weights

Lister hooded female rats, fed palatable high energy foods and chow, weighed significantly more than chow-fed control rats before mating. A smaller proportion of the obese rats became pregnant, and they lost more litters in lactation. When litters survived (7±1 pups), maternal weight changes differed between groups during lactation. The controls gained 6.2±3.2 g, whereas the obese rats lost variable amounts of weight despite the continued availability of the palatable diet. The rats that were heaviest at mating and parturition and which showed the largest non-fetal weight gains in pregnancy (i.e., the “large weight loss group”) lost 60.6±4.8 g, while less obese rats which showed similar non-fetal gains to controls (i.e., the “small weight loss group”) lost 24.6±3.2 g. Thus the weights of all groups converged and were similar after three weeks of lactation, but diverged again after weaning. During lactation the total energy intakes and amounts of protein consumed by the obese rats were significantly below those of controls, and total fat intake was significantly elevated. Although litter size and pup weights did not differ significantly at birth, pups of obese mothers weighed significantly less than those of controls at weaning. Maternal obesity in lactation appears to influence both body weight regulation and lactational performance.     

Altered orosensory sensitivity to oils in CCK-1 receptor deficient rats

CCK-1 receptor deficient Otsuka Long Evans Tokushima Fatty (OLETF) rats are hyperphagic, which leads to subsequent obesity and diabetes. Additionally, they have increased sham intake and enhanced preference for sucrose solutions relative to control, Long Evans Tokushima Otsuka (LETO) rats. To determine the effects of oil on ingestion, we first measured real feeding of various concentrations of oil emulsions (12.5, 25, 50, 75, and 100%) in rats that were fed ad libitum. Secondly, to isolate the orosensory compontent of oils from post-ingestive consequences, as well as determine the contribution of energy status, we measured sham feeding in OLETF and LETO rats using one-bottle acceptance tests while non-deprived and overnight food deprived. Finally, to assess the orosensory effects of nutritive and non-nutritive oils, we used two-bottle preference tests in sham fed OLETF and LETO rats. We found that real feeding resulted in increased intake of high oil concentrations for OLETF rats relative to LETO rats. Similarly, OLETF rats consumed significantly more of higher concentration corn oils than LETO while non-deprived sham feeding. Conversely, OLETF rats overconsumed low concentration corn oil compared to LETO during overnight deprived sham-feeding tests. In two-bottle sham-feeding preference tests, both non-deprived OLETF and LETO rats preferred corn to mineral oil. Collectively, these results show that increased oil intake in OLETF rats is driven by both peripheral deficits to satiation and altered orosensory sensitivity.     

Effect of treadmill exercise on food intake and body weight in lean and obese rats

Body weight and food intake of lean and obese, male and female Osborne-Mendel rats following treadmill exercise were compared. Rats were assigned, separately by sex, to one of three diet groups; Group 1 was fed a low fat (10%) diet throughout the study, Group 2 was fed a high fat (55%) diet for 16 weeks and then switched to the low fat diet 1 week prior to exercise, and Group 3 was fed the high fat diet throughout the study. To control for differences in work output between the leanest and heaviest animals, exercise intensity was adjusted across groups such that all exercised rats had equivalent energy expenditure. After a 3 day training period, the exercise was successively increased over 8 days until a work output of 374.9J was reached. Relative to their respective controls, obese exercised males showed a reduction in body weight but no change in food intake. In contrast, exercised females showed no change in body weight or food intake, regardless of dietary condition.     

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.     

Evidence from catch-up growth and hoarding behavior of rats that exposure to hypobaric air lowers the body-mass set point

The depression of body growth rate and the reduction of body mass for chronological age and gender in growing experimental animals exposed to hypobaric air (simulated high altitude = SHA) have been associated with hypophagia because of reduced appetite. Catch-up growth during protein recovery after a short period of protein restriction only occurs if food intake becomes super-normal, which should not be possible under hypoxic conditions if the set-point for appetite is adjusted by the level of SHA. The present investigation was designed to test the hypothesis that growth retardation during exposure to SHA is due to an alteration of the neural mechanism for setting body mass size rather than a primary alteration of the central set-point for appetite. One group of female rats aged 35 d were exposed to SHA (5460m) in a SHA chamber for 27 d (HX rats). Other group was maintained under local barometric pressure conditions (NX rats). One half of both NX and HX rats were fed a protein-free diet for the initial 9 d of the experimental period. From this time on, they were fed a diet containing 20% protein, as were the remaining rats of both groups during the entire experimental period. The growth rates of both mass and length of the body were significantly depressed in well-nourished rats exposed to SHA during the entire observation period when compared to normoxic ones. At its end, body mass and body length were 24% and 21% less in HX than in NX rats. Growth rates were negatively affected by protein restriction in both NX and HX rats. During protein recovery, they reached supernormal values in response to supernormal levels of energy intake that allowed a complete catch-up of both body mass and length. The finding that energy intake during the period of protein rehabilitation in HX rats previously stunted by protein restriction was markedly higher than in HX control ones at equal levels of hypoxia demonstrates that the degree of hypoxia does not determine directly the degree of appetite and energy intake. Furthermore, the finding that catch-up growth in the stunted HX rats returns the animal only to the stunted size appropriate for the hypoxic animal supports the hypothesis that hypoxia lowers the set-point for body mass size, which is reached by inhibition of appetite. Confirmation of the hypothesis was done by assessment of the set-point of body mass by the behavioral method of the weight threshold to hoard food. It was lowered by 17.0% in HX rats.     

Quantity not composition of dietary fats represents the dominant contributor to experimental obesity: Relevance to human pathophysiology

Plant fats are low in saturated fats but high in unsaturated fats compared to animal fats, and are supposedly less obesogenic. This study compared the obesogenic effects of plant and animal derived fatty diets in Wistar rats. Rats of each gender were divided into three dietary (standard chow (SC), high fat diet rich in animal fat (HFDaf) and a high fat diet rich in plant fat (HFDpf)) groups of ten each and fed for 17 weeks. Anthropometric, Adiposity and nutritive variables were assessed using standard methods. Comparing HFDpf to HFDaf: Abdominal circumference (AC),initial feed intaken (IFI), final feed intake(FFI), final body weight (FBW), white adipose tissue (WAT) were increased but brown adipose tissue (BAT) decreased in male rats fed with HFDpf; also, there were increased body length, IFI, FFI but decreased AC, FBW, BAT in female rats fed with HFDpf. Comparing male to female rats: Thoracic circumference, IFI, FFI, energy intake were increased while Adiposity index decreased across diet groups in male rats; the AC, FBW increased while WAT, BAT decreased in HFDpf fed group, also, BAT was increased but AC, FBW decreased in HFDaf fed group in male rats. Palatability and high feed efficiency of consumed diets were more associated with obesogenic risk than just the level of saturation. Therefore, Obesogenic effects of fatty diets in both genders is more dependent on the quantity (amount) of fatty diet consumed than the dietary fat composition alone.     

Inverse relationship between brown fat thermogenesis and meal size: The thermostatic control of food intake revisited

This study examines a new hypothesis whereby heat production from brown fat in response to eating may serve as a feedback signal for satiety. To test this hypothesis, in vitro respiration rate of brown adipose tissue (BAT) was determined in relation to the voluntary caloric intake of the preceding test meal. This relationship was examined as a function of meal composition and of obesity. It was found that in rats fed a high fat diet, as well as in two types of obese rats (VMH and Zucker), respiration rate per 100 mg tissue was significantly reduced, and energy intake of the preceding test meal increased compared to rats receiving a low fat diet or to respective lean rats. These data lend support to a brown fat mediated thermostatic hypothesis for the control of food intake.     

Hypothalamic hyperphagic rats overeat bitter sucrose octa acetate diets but not quinine diets.

Female rats were made hyperphagic with knife cuts or lesions in the ventromedial hypothalamus (VMH) and their aversion to food made bitter by adulteration with quinine or sucrose octa acetate (SOA) was examined. In short-term choice tests VMH obese rats, as well as controls, strongly preferred a 0.1% quinine diet to a 1.0% SOA diet. Yet, in 24 hr intake tests VMH obese rats overate, relative to controls, the 1% SOA diet, but underate the 0.1% quinine diet. VMH rats in both dynamic and static stages also overate SOA diets in concentrations up to 16%. However, VMH obese rats underate a 1% SOA diet when previously fed a 0.1% quinine diet. The results indicate that the VMH rat's finickiness to quinine diets may not be due to bitter taste alone, but may result from toxic postingestive effects of quinine and the development of a conditioned taste aversion.     

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.     

Energy intake of rats fed a cafeteria diet

The proportion of lipid, carbohydrate and protein energy self-selected by male and female rats from a cafeteria diet has been studied for a 48-day period (36-day in female rats). The diet consisted in 12 different items and was offered daily, in excess and under otherwise standard conditions, to rats--caged in groups of three--from weaning to adulthood. Groups of control animals were studied in parallel and compared with the cafeteria groups. Cafeteria diet fed groups of rats ingested more energy and lowered their metabolic efficiency with age. Male rats ate more than females and increased their body weight even after female practically stopped growing. There was a wide variation in the aliments consumed each day by the cafeteria-fed rats. However, the proportion of lipid, protein and carbohydrate the rats ate remained constant. Male rats ingested more lipid than females. Carbohydrate consumption was constant in control and cafeteria fed groups of rats independently of sex. Protein consumption was higher in cafeteria rats than in controls, but the differences were not so important as with liquid. Fiber content of the cafeteria diet was lower than that of the control diet. The cafeteria diet selected by the rats was, thus, hypercaloric and hyperlipidic, with practically the same amount of carbohydrate than the control diet, slightly hyperproteic and, nevertheless, remarkably constant in its composition with respect to time. Cafeteria rats had a higher water intake than controls. All these trends were maintained despite the observed changes in the animals' tastes and their differential consumption of the ailments of the diet.     

Dietary obesity in exercising or cold-exposed Syrian hamsters

High-fat diet-feeding increases body weight and adiposity in Syrian hamsters (Mesocricetus auratus), effects due in part to decreased energy expenditure. The effects of voluntary exercise- or cold exposure-induced increases in energy expenditure were examined in fat- or chow-fed, female Syrian hamsters. In Experiment 1, voluntary exercise (10 weeks) caused a moderate hyperphagia and actually increased body weight in both diet groups through increases in lean body mass. Carcass lipid was not affected by by exercise in chow-fed hamsters and only slightly reduced in fat-fed animals. In Experiment 2, chronic (8 weeks) cold exposure (5 degrees C) increased energy intake to the same extent in both dietary groups relative to the warm-exposed (23 degrees C) controls. High-fat diet-induced obesity was largely prevented by cold exposure. Cold exposure reduced lean body mass in chow-fed hamsters, but this carcass component was spared by fat-feeding. These results indicate that the increased metabolic demands of cold exposure were more effective in preventing this form of diet-induced obesity than those of voluntary exercise (80% and 17% reductions in carcass lipid, respectively). These results are discussed in terms of possible beneficial effects of eating a lipid-rich diet prior to winter.     

Regulation of feeding behavior in the prepubertal female rat.

Responses to challenges of long-term regulation of feeding behavior were compared between adult and weanling female rats. Adulteration of a high fat diet with NaCl caused both adult and weanling rats to reduce their food intake, but neither group refused to eat. Food deprivation for 24 hr was followed by an increase in feeding for both adult and weanling animals during a period when food intake is normally very low. Continued limited food access to 2 hr during the light period was compensated for by an increase in the normal food intake for this period for both adult and young female rats. It was observed that both adult and weanling rats showed a marked preference for the more dilute glucose solution when given a choice. In addition, both groups maintained a constant caloric intake during presentation of the glucose solutions by adjusting their intake of a solid food source. In each challenge of long-term regulation of feeding behavior, the response of weanling animals was as good or superior to that shown by adults. It is concluded that weanling female rats regulate their feeding just as adults to maintain long-term energy balance. It was also observed that bilateral lesions placed in the ventromedial hypothalamus (VMH) at 21 days of age resulted in reduced daily food intake and retarded body weight gain. Furthermore, young rats with VMH lesions failed to respond to 24 hr of food deprivation or limited food access. These data suggest an important role for the VMH in the long-term regulation of feeding in young rats.