Neurological and stress related effects of shifting obese rats from a palatable diet to chow and lean rats from chow to a palatable diet

Rats exposed to an energy rich, cafeteria diet overeat and become obese. The present experiment examined the neural and behavioural effects of shifting obese rats from this diet to chow and lean rats from chow to the cafeteria diet. Two groups of male Sprague Dawley rats (n = 24) were fed either highly palatable cafeteria diet or regular chow (30% vs. 12% energy as fat) for 16 weeks. Half of each group (n = 12) was then switched to the opposing diet while the remainder continued on their original diet. The effects of diet switch on the response to restraint stress were assessed and rats were euthanised nine days after diet reversal. After 16 weeks of cafeteria diet, rats were 27% heavier than controls. Rats switched from chow to cafeteria diet (Ch–Caf) became hyperphagic and had increased dopamine D1, D2 and tyrosine hydroxylase mRNA expression in the ventral tegmental area (VTA) compared to rats switched from cafeteria to chow (Caf–Ch). Caf–Ch rats were hypophagic with significant reductions in white (16%) and brown (32%) adipose tissue mass, plasma leptin (34%) and fasting glucose (22%) compared to rats remaining on the cafeteria diet (Caf–Caf). Caf–Caf rats had an elevated plasma corticosterone response to restraint stress compared to Ch–Caf rats indicating that acute but not chronic consumption of palatable cafeteria diet may protect against stress. Caf–Ch rats had increased corticotropin releasing hormone mRNA expression in the dorsal hypothalamus compared to Ch–Ch rats implying that removal of the palatable diet activated the HPA axis. The results were discussed in terms of the links between palatability of diet, obesity and stress.     

Returning 'cafeteria-fed' rats to a chow diet: negative contrast and effects of obesity on feeding behaviour

Two experiments examined the feeding behaviour and body weight changes of rats returned to a standard chow diet after prolonged periods of cafeteria feeding. In the first, both overweight (ad lib fed) and 'normal' weight (fed a restricted ration of cafeteria foods) cafeteria rats became hypophagic compared to chow-fed rats following their return to chow feeding. However, the overweight rats' hypophagia was initially more severe and was longer lasting. In the second experiment, analysis of meal patterns recorded throughout the first 4 weeks on chow after 26-32 weeks of ad lib cafeteria feeding showed that the hypophagia was due to a reduction in mean meal size (MMS) and meal frequency (MF). Food intake and MMS subsequently recovered to within control levels (by 2-3 weeks), but MF remained persistently low. There was a decrease and then a recovery in eating rate (ER) which paralleled the changes in MMS. The previously cafeteria-fed rats lost only 60% of their excess body weight. These findings are interpreted in terms of a negative contrast effect (changes in MMS and ER) and an inhibitory action of increased adiposity on feeding (affecting mainly MF).     

Effects of early life interventions and palatable diet on anxiety and on oxidative stress in young rats

Early life events can change biochemical, endocrine and behavioral aspects throughout the life of an animal. Since there is a strong relationship between stress, neonatal handling and feeding behavior, the aim of this study was to investigate the effects of these three factors on behavioral parameters (anxiety and locomotion), oxidative stress in brain structures (prefrontal cortex and hippocampus) and on plasma glucose. Nests of Wistar rats were handled (10 min/day), or not (control groups), on days 1-10 after birth. Males from these groups were divided into 4 subgroups: (1) stressed by isolation in childhood (pre-puberty) and with access to a highly palatable diet (2) stressed by isolation and receiving standard lab chow (3) not isolated and receiving a highly palatable diet and (4) not isolated and receiving standard chow. The animals were kept under these conditions for 7 days. Rats receiving the highly palatable diet consumed more food, more calories, gained more weight and had a higher plasma glucose level, but had a lower caloric efficiency than the standard chow groups. Both handling and palatable diet were able to increase food consumption on the first day of isolation. Isolation stress had an anxiogenic effect in the plus maze, which was counteracted by handling. Palatable diet increased time spent in the central area of the open field apparatus and in the open arms of the elevated plus maze, showing an anxiolytic effect. The use of both these conditions, however, does not appear to bring additional protection against the effects of stress during this particular period of life, i.e., pre-puberty. In the prefrontal cortex, handling reduced thiol content and appears to imbalance the antioxidant enzymes system, which is counteracted by a palatable diet. Hippocampus seems to be more sensitive than the prefrontal cortex to early interventions, especially to the highly palatable diet, and both handling and diet appear to imbalance the antioxidant enzyme system. Thus, measurements of antioxidant enzymes activities indicate that handling may endanger some brain structures and that the palatable diet was able to prevent some handling effects on antioxidant enzymes, depending on the brain structure.     

Effects of a gastric implant on body weight and gastrointestinal hormones in cafeteria diet obese rats

In order to evaluate the effectiveness of a gastric implant in an animal model of dietary obesity, silicone implants (2.5 ml) were inserted into the stomachs of male rats maintained on a chow or "cafeteria" diet. At the time of implantation, the cafeteria fed rats weighed 14% more than chow fed controls. Overweight cafeteria fed animals lost weight in response to the gastric implant, whereas control chow fed animals did not. Both implant groups had significant increases in stomach weights in contrast to sham implant groups, but the increase was much less in the cafeteria diet group. The fasting plasma levels of the gastrointestinal hormones, gastrin and pancreatic polypeptide, and oxytocin (a marker of vagal afferent function) were measured by radioimmunoassay. Cafeteria fed sham or implanted animals had significantly higher fasting levels of plasma oxytocin and gastrin, and significantly lower plasma levels of pancreatic polypeptide than the chow fed groups. These studies demonstrate that the gastric implant has more effect on weight in overweight animals on a palatable mixed diet, perhaps related to both mechanical and neural factors.     

Hyperactivity and obesity: The interaction of social isolation and cafeteria feeding

Rats were reared in social isolation or in social groups of 4 or 5 rats per cage from weaning and were fed either a lab chow diet or a diet of 4 palatable foods (cafeteria diet), in addition to the lab chow. The hyperactivity of isolation-reared rats appears to be a reactivity to novel environmental stimuli, since it was seen only in the 0.5 hr tests and not in the near 24 hr test. It was found that hyperactivity and increased body weight can develop within as few as 7 to 10 days in rats reared in isolation from weaning. Cafeteria feeding enhanced activity in isolation-reared rats, but suppressed it in group-reared rats. Isolation-reared rats fed a cafeteria diet had strong, stable preferences for their most preferred food over the 25 days of measurement. Rats reared in isolation had significantly different food preferences, as compared with rats reared in groups. Cafeteria fed rats had a significantly greater calorie intake and body weight than rats fed lab chow. On analysis, cafeteria fed rats had significantly greater carcass energy and an increased amount of parametrial white adipose tissue as compared with rats fed only lab chow. The interscapular brown adipose tissue (IBAT) weights of cafeteria fed rats were also greater. However, as there was no difference between the cafeteria and chow fed rats in the total amount of protein in the IBAT, it was concluded that the increased weight of the IBAT did not reflect a genuine hypertrophy of the tissue.     

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.     

Effects of diet composition on food intake and carcass composition in rats

Since most of the weight-reduced obese humans are in a protein deficit state, this study was designed to examine whether a high protein diet (HP) enhances the restoration of lean body mass and facilitates the maintenance of weight loss. Obesity in rats was produced by 16 weeks of high fat diet (HF) feeding. In the 17th week, all HF-fed obese rats were fed a limited amount of control diet to normalize their body weights, but they still had more body fat content. The HF-fed rats were then divided into subgroups with different diets offered for 5 weeks: HP, HF or chow diet. A control group was fed the chow diet throughout the study. HP feeding maintained normal body weight and carcass composition in weight-reduced obese rats by reducing feeding efficiency levels to within normal ranges. Weight-reduced rats fed a chow diet, however, had more fat mass than controls and HF feeding stimulated weight gain again. Therefore, a HP diet has a higher probability of enhancing weight loss maintenance in weight-reduced obese subjects than does a usual well-balanced diet.     

Effects of diet and exercise training on thermogenesis in adult female rats

The effects of a cafeteria diet on body weight gain, food intake, resting metabolic rate (RMR) and the thermic effect of food (TEF) were compared in female Charles River albino rats that were either sedentary or exercise-trained. The food intakes of the exercise-trained rats on the cafeteria diet were increased to the same degree as those of the sedentary rats, however, they gained less body weight and body fat than sedentary controls. The exercise training increased RMR independent of diet, but differentially increased TEF in rats given the cafeteria diet. Conversely, sedentary rats on the cafeteria diet had significantly lower RMR, but their TEF were not different from control animals on lab chow. Thus, in addition to the direct cost of the exercise, training increased thermogenesis (RMR and TEF) which also helped prevent the dietary obesity which normally occurs with cafeteria diets.     

A maternal cafeteria diet during gestation and lactation promotes adiposity and impairs skeletal muscle development and metabolism in rat offspring at weaning

We examined the effects of a maternal cafeteria diet on skeletal muscle and adipose tissue development in the offspring at weaning. Rats born to mothers fed the cafeteria diet either during gestation alone or during both gestation and lactation exhibited a 25% reduction in muscle cross-sectional area with approximately 20% fewer fibres compared with pups fed a balanced chow diet. Maintaining the cafeteria diet during lactation increased intramuscular lipid content and fat pad weights characterized by adipocyte hypertrophy but not hyperplasia. These pups also had elevated muscle IGF-1, IGF-1 receptor, and PPARγ mRNA levels, which may indicate an attempt to maintain normal insulin sensitivity. The increased adiposity and elevated IGF-1, IGF-1 receptor and PPARγ mRNAs were not seen in the pups rehabilitated to the balanced diet during lactation. However, these pups exhibited reduced muscle cell proliferation (PCNA) with reduced insulin receptor and a trend towards reduced glucose transporter (GLUT)-4 mRNAs when compared with pups fed a balanced chow diet, indicating possible alterations in glucose uptake by muscle tissue. Therefore, rats born to mothers fed a cafeteria diet during gestation alone or during both gestation and lactation exhibited impaired skeletal muscle development and metabolic disorders normally associated with insulin resistance as early as the weaning stage.     

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.     

Overeating, overweight and obesity induced by an unpreferred diet

Rats fed diets containing 50-71% added water (liquid diets) eat more energy and gain more weight than rats fed the same diets without added water (solid diets). The present experiments examined the effects of making a liquid diet less palatable. The first experiment examined the effects of sucrose octaacetate on diet preference. Rats, given a choice of a liquid diet containing 0.5% sucrose octaacetate and a plain solid diet, preferred the plain solid diet for three weeks. When the concentration of sucrose octaacetate was reduced to 0.05%, the rats did not show a reliable preference for either the sucrose octaacetate liquid or plain dry diet. In subsequent experiments, each rat was given only one diet at a time. In the second experiment, rats were fed 0.5% sucrose octaacetate liquid diet for three weeks followed by 0.05% sucrose octaacetate liquid diet for another four weeks. The rats fed the sucrose octaacetate liquid diet overate and became obese compared to the rats fed plain solid diet throughout. In the third experiment, rats fed 0.5% sucrose octaacetate liquid diet for six weeks became obese compared to rats fed plain solid diet throughout. Thus, the overeating and obesity induced by liquid diets cannot be attributed solely to their high palatability.     

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.     

Effects of diet and obesity on body weight regulation during pregnancy and lactation in the rat

The effects of obesity level and cafeteria feeding were studied in rats during pregnancy and lactation. The non-fetal weight gain in pregnancy was three times greater with the cafeteria diet than with chow, indicating that fat deposition is not regulated at an optimal level during pregnancy. There was a strong negative correlation between postpartum weight and weight change during lactation. Obese rats were finicky in that their weight changes in lactation were exaggerated when the diet was changed between pregnancy and lactation. Pup growth rate was proportional to maternal energy intake but in this experiment not related to maternal protein, fat or carbohydrate intake. In obese rats switched to chow, intake was inadequate for normal pup growth. Thus, the weight gains in pregnancy are not regulated at a set level, and the weight change in lactation appears to compensate for the weight gain in pregnancy.     

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.     

Reduced accumbens dopamine in Sprague-Dawley rats prone to overeating a fat-rich diet

Obese humans and animals exhibit reduced functioning of the dopamine (DA) system in the nucleus accumbens (NAc). The question addressed here is whether this change in NAc DA can be detected in Sprague-Dawley rats that are prone to obesity on a fat-rich diet but still at normal body weight. Rats were subgrouped as “obesity-prone” (OP) or “obesity-resistant” (OR), based on their weight gain during 5 days of access to a high-fat diet, and were then shifted to a lower-fat chow diet before microdialysis testing was performed. The OP rats compared to OR rats exhibited markedly reduced basal levels of DA in the NAc. After a high-fat challenge meal, both OP and OR rats showed a significant increase in extracellular DA and its metabolites; however, the NAc DA of the OP rats still remained at reduced levels. Also, the increase in DA and metabolite levels observed in OR rats after systemic administration of a fat emulsion was not evident in the OP rats, which instead showed no change in DA and a decrease in its metabolites. These results demonstrate, first, that fat can stimulate accumbal DA release and, second, that outbred rats prone to overeating and becoming obese on a palatable, fat-rich diet exhibit reduced signaling in the mesolimbic DA system while still at normal weight, suggesting that it may be causally related to their excess consummatory behavior.     

Differential effects of chow and purified diet on the consumption of sucrose solution and lard and the development of obesity

Obesity has been associated with increased consumption of sweetened beverages and a high-fat diet. We determined whether the composition of the dry pellet offered with liquid sucrose (LS) and lard influenced the development of obesity. We hypothesized that animals offered LS or LS and lard (choice), in addition to chow or purified low fat diet pellet (LFD; 10% fat), would gain more body fat than controls. We compared the effects of LFD vs. chow on voluntary consumption of LS and lard, serum triglyceride (TG), glucose, and body fat over 21 days. Male Sprague Dawley rats (n=10/group) were offered chow, chow+LS, chow choice, LFD, LFD+LS, LFD choice or solid high-sucrose diet (70% sucrose). Energy intakes of rats fed chow, LFD, and high-sucrose diets were similar. Energy intake was increased by 16% in chow+LS, 15% in LFD+LS, 11% in LFD choice, and 23% in chow choice rats. Chow choice rats consumed 142% more lard than LFD choice rats. Fasting glucose increased in all choice rats compared with the chow and high-sucrose diet rats. Fasting TG increased in LFD choice rats and were ~75% higher than those of chow, LFD, or high-sucrose rats. Chow choice had higher carcass fat than chow, chow+LS, and LFD groups however LFD choice was not different from their controls. Another experiment confirmed rats consumed 158% more lard when given chow choice compared to LFD choice. The diet offered to rats with free access to LS and lard influenced the development of obesity, sucrose and lard selection, and TG.     

Diverse basal and stress-related phenotypes of Sprague Dawley rats from three vendors

Based on observed phenotypic differences in growth and ACTH responses to stress in Sprague Dawley rats obtained from different vendors, we ran head-to-head comparisons on rats obtained from three different vendors, Harlan, Charles River, and Simonsen, with respect to baseline phenotypic differences and a metabolic feedback hypothesis of hypothalamo-pituitary-adrenal (HPA) regulation. Charles River and Harlan rats gained weight faster than Simonsen rats, but chow intake standardized for body weight was not increased, consistent with their greater caloric efficiency. Weight gain was inversely related with mean daily temperatures, without differences in activity levels. Half of the animals given lard and 32% sucrose solutions in addition to chow increased caloric intake and core temperature, decreased caloric efficiency, and increased fat depots, leptin, and in Simonsen rats, insulin. A 5-day regimen of once-daily 2-h restraint decreased feeding and caloric efficiency. Rats from two vendors with the availability of sucrose and lard, Charles River and Simonsen, showed blunted HPA responses to restraint compared to chow controls, whereas the Harlans exhibited no adrenocorticotropin (ACTH) response and an amplified adrenocortical response on the high-energy diet compared to chow controls. Substantial phenotypic differences exist between Sprague Dawley rats from different vendors with respect to metabolism and HPA function. The metabolic feedback hypothesis was supported in two of the three vendors' rats.     

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.     

Analysis of a conflict between palatability and cold exposure in rats

Rats were trained to feed each day from 10 o'clock to 12 noon. Once a week in an environment of Ta--15 degrees C, additional food was made available 16 m from a thermoneutral refuge. The additional food offered was either shortcake, meat paté, peanut butter, Coca-cola, all of these (cafeteria), or laboratory chow. Although laboratory chow was also always available in their thermoneutral home, rats invariably ran in the cold to the feeder, especially so when the food offered was highly palatable. With such foods, animals took as much as half their nutrient intake in the cold. For less palatable food, rats went only once or twice to the feeder, and there ate little. The attractiveness of the various foods was ranked similarly by the amount eaten, the number of excursions to the feeder, and the time spent feeding in the cold. Meal duration and speed of running to the food were not influenced by palatability. For the whole group, the preference was: shortcake, Coca-cola, meat paté, peanut butter, and chow. There was a considerable variation between rats in their attraction to different foods. Feeding behavior in a situation of conflict could be used to measure palatability.     

Changes in actual versus defended body weight elicited by a varied, palatable ("supermarket") diet in rats

Male rats fed on a varied, palatable supermarket diet for 11 weeks gained more weight than chow-fed controls. When palatable food was discontinued, their body weights became static, but remained significantly higher than control weights for a further 5 weeks. Hoarding of food was readily elicited by food deprivation in the dietarily obese as well as in the chow-fed rats. Previous studies have shown that the critical body weight at which hoarding appears does not covary with body weight, but appears to reflect a defended level of body weight. In the present study, critical weights were not significantly different between groups before supermarket diet, but were significantly higher in the supermarket rats after obesity had developed. Thus, the increase in body weight brought about by a supermarket diet (unlike that in ventromedial hypothalamic obesity) can be accompanied by an increase in the defended level of body weight as inferred from the critical weight for the onset of hoarding behaviour.