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.     

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.     

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.     

Early onset of obesity induces reproductive deficits in female rats

The incidence of obesity is increasing rapidly all over the world and results in numerous health detriments, including disruptions in reproduction. However, the mechanisms by which excess body fat interferes with reproductive functions are still not fully understood. After weaning, female rats were treated with a cafeteria diet or a chow diet (control group). Biometric and metabolic parameters were evaluated in adulthood. Reproductive parameters, including estradiol, progesterone, LH and prolactin during the proestrus afternoon, sexual behavior, ovulation rates and histological analysis of ovaries were also evaluated. Cafeteria diet was able to induce obesity in female rats by increasing body and fat pad weight, which resulted in increased levels of triglycerides, total cholesterol, LDL and induced insulin resistance. The cafeteria diet also negatively affected female reproduction by reducing the number of oocytes and preantral follicles, as well as the thickness of the follicular layer. Obese females did not show preovulatory progesterone and LH surges, though plasma estradiol and prolactin showed preovulatory surges similar to control rats. Nevertheless, sexual receptiveness was not altered by cafeteria diet. Taken together, our results suggest that the cafeteria diet administered from weaning age was able to induce obesity and reduce the reproductive capability in adult female rats, indicating that this obesity model can be used to better understand the mechanisms underlying reproductive dysfunction in obese subjects.     

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.     

Wistar rats allowed to self-select macronutrients from weaning to maturity choose a high-protein,high-lipid diet

The aim of this work was to study the evolution of rat food choice in relation to their age and metabolic parameters. Eighty Wistar rats were studied from birth to 13 weeks of age. At weaning, six litters were fed on a macronutrient self-selecting diet and four on a standard diet. In self-selecting males, protein intake was maximal at Week 7 of age and then plateaued (Week 13), whereas in females, protein consumption peaked at Week 7 and then steadily decreased. Females showed a strong and early preference for fat, which increased continuously with age. Males and females ingested their total energy intake during the dark period (respectively, 79% and 70%). Simple meals (composed of one item) were mainly ingested during the light phase, while mixed meals (at least two items) were ingested during the night. In males, most mixed meals began with carbohydrate bouts and finished with proteins, while in females no particular choice was observed at the beginning of meals, but most of them ended with protein bouts. Body weights of either male and female self-selecting or control fed rats were not significantly different at the end of the experiment. Differences between dietary groups in body fat mass were not observed with the exception of higher subcutaneous fat found in self-selecting rats. Moreover, insulinemia was lower in both male and female self-selecting rats. The high-protein, high-fat diet chosen by the self-selecting rats could be linked to a prevention of the age-related insulin resistance.     

Dietary obesity in adult and weanling rats following removal of interscapular brown adipose tissue

In order to investigate the role of brown adipose tissue (BAT) in diet-induced thermogenesis (DIT), a selection of palatable, energy-dense foods (Cafeteria diet) was used to increase the energy intakes of adult and weanling male rats, from some of which interscapular BAT (IBAT) had been surgically excised. Removal of IBAT had no effect upon energy intakes of the cafeteria-fed rats, nor of controls fed a pelleted stock diet. The rate of weight gain of intact controls was similar for the two diets, but adults with IBAT removed and fed with the cafeteria diet gained weight more rapidly than those fed the stock diet. Similarly, although intact weanlings did not exhibit excess weight gain when fed the cafeteria diet, removal of IBAT did result in more rapid weight gain of the cafeteria-fed weanlings relative to their stock-fed siblings. Nevertheless, total carcass energy was increased by some 20% in cafeteria-fed animals, irrespective of whether they had had IBAT removed. Thus there was no evidence for removal of IBAT having improved the efficiency of energy utilisation for growth. The failure to find evidence for altered levels of energy expenditure following removal of IBAT does not necessarily contradict the hypothesis that BAT mediates DIT, however, since, following removal of IBAT, there was hypertrophy of remaining BAT sites which may have compensated for the BAT removed.     

Effects of alternations (10 days) of high-fat with normal diet on liver lipid infiltration, fat gain, and plasma metabolic profile in rats

The purpose of the present study was to test the hypothesis that short-term alternations of high-fat with normal chow feeding result in higher fat accumulation in liver than continuous intake of the same high-fat diet. Male Sprague-Dawley rats (7 weeks of age) were divided into 3 groups according to diet composition: standard chow (SD; 12,5% kcal as fat), high-fat (HF; 42% kcal as fat), and food cycles (FC) consisting of 10-day alternations between HF and SD diets beginning with the high-fat diet. Rats in each of these 3 groups were sacrificed after 10, 30, and 50 days (n = 10 rats/sub-groups). Energy intake, body weight, liver and muscle relative weights were not significantly (P > 0.05) different between FC- and HF-fed rats. Using the total energy intake for the 50-day period, it was calculated that approximately 30% less calories as fat was ingested in the FC- compared to the HF-fed rats. In spite of this, liver lipid infiltration as well as fat accretion in abdominal adipose tissues were increased (P < 0.01) similarly in FC- and HF-fed rats. Plasma FFA and insulin levels depicted strong tendencies (P < 0.07) to be higher in FC- than in continuous HF-fed rats at the end of the 50-day period. These results indicate that, despite a 30% reduction in ingested lipids, alternations of HF with normal chow diet compared to the continuous hyperlipidic diet caused the same level of infiltration of lipids in the liver and in the abdominal adipose tissues and, to a certain extent, may even result in a larger deterioration of the metabolic profile.     

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.     

Does intestinal absorption participate in the ponderostat?

Body weight regulation is known to achieve energy balance through several responses: appetite, satiety, thermogenesis, feeding behavior. Absorption efficiency might be, also, another response. In this paper, we hypothesized that the intestinal absorption efficiency of the rat might be lowered in response to a high energy content of the diet. Thirty-one rats were assigned to a specific diet (restricted, control, and cafeteria) during three weeks. Rats' body mass, BMI, and body fat were measured and absorption efficiency was calculated through the ratio of energy ingested/energy defecated. Intestinal histology was examined post-mortem. Absorption efficiency was not lower in cafeteria groups but was higher than in control and restricted rats. No histological difference was seen after the various diets. Such results indicate that intestinal absorption is working at full efficiency whatever the diet, and is not a regulatory response contributing to the ponderostat.     

Alleviation in the rat of a GABA-induced reduction in food intake and growth

Cold exposure and diet dilution which stimulate food intake of normal rats lessened depressions of food intake and growth induced by dietary GABA. During a 3-day adaptation to the cold, rats fed a diet containing 4.5% GABA lost weight; thereafter, food intake and growth rate differed little from those of cold control rats and were usually greater than those of normal rats fed GABA. Hepatic GABA-aminotransferase activity of cold-exposed rats fed the GABA diet increased to about twice that of normal control rats. Rats fed a control diet diluted by half with cellulose ate 50% more of this diet than of the undiluted diet but gained only 20% less weight. Rats ate twice as much of a diluted, 9% GABA diet as of an undiluted, 4.5% GABA diet (thus doubling their GABA intake) and gained three times as much weight. A novel food (condensed milk) barely lessened the adverse responses to GABA. These results show that conditions requiring rats to increase their food intake in order to maintain body weight can also increase their acceptance of a diet high in GABA.     

Effects of unpalatable diets and food restriction on feed efficiency in growing rats

During a 15-day experiment, weanling rats fed a 10% casein diet adulterated daily by one of four aversive taste stimuli ate 12–16% less than their controls fed ad lib on the unadulterated diet. They also demonstrated an inhibition in feed efficiency (g body weight gain/g food intake) during the first 8 days. A second control group, pair-fed to the group receiving the adulterated diet, also showed a reduction in feed efficiency. By Day 9, a compensatory process was evident in the rats fed the unpalatable diet such that feed efficiency increased above that observed for the ad lib control group. By the end of the experiment all three groups exhibited the same efficiency. The ratio of urinary nitrogen to total nitrogen intake was higher in rats fed the unpalatable diet ad lib compared to those offered the unadulterated diet ad lib. This observation suggests that the rats on the unpalatable diet were using more of the dietary protein as a caloric source than were their controls.     

Chronic food restriction and reduced dietary fat: risk factors for bouts of overeating

The purpose of this study was to determine the effect of chronic food restriction and reduced dietary fat on feeding behavior and body weight. Young female rats were fed ad lib or food restricted on a low-fat (LF) or a fat-free (FF) diet for 4 weeks. Rats then received 24-h free access to 2 diets, the maintenance diet (LF or FF) plus a novel high-fat (HF) diet (24-h intake test). After the test, all the rats were allowed chronic free access to the HF diet until body weight was stable. During the 24-h test, the restricted groups ate significantly more calories than the ad lib groups, and the FF-restricted rats ate significantly more total food, carbohydrate and protein than the LF-restricted rats; there were no differences between the two ad lib groups. During chronic free access to the HF diet, the formerly restricted rats achieved and defended lower body weights than the formerly non-restricted rats. Throughout the experiment, the ad lib groups had more body fat than the restricted groups independent of the dietary subgroup. Hence, a history of chronic food restriction predisposes to consuming more food in acute feeding situations, particularly when dietary fat is reduced, and lowers the level of body weight maintained and defended. Chronic food restriction accompanied by reduced dietary fat may increase risk for bouts of overeating.     

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.     

Dietary fructose produces greater nephrocalcinosis in female than in male magnesium-deficient rats

The synergistic interaction of fructose and magnesium (Mg) deficiency on kidney calcification was compared in male and female rats. Male and female weanling rats were divided into four dietary groups: fructose or starch, with or without Mg. Rats were fed their respective diets for 9 weeks, and 24 h urine was collected to measure urinary output, pH, Mg, calcium (Ca), and oxalic acid. Rats were fasted overnight. After decapitation, blood was collected immediately, and kidneys were removed to determine their Mg and Ca content. Dietary fructose significantly increased kidney Ca in female rats fed deficient or adequate Mg diet and in male rats fed Mg-deficient diet only; the greatest kidney calcification occurred in female rats fed Mg-deficient diet (P less than 0.0001). Even in starch groups female rats fed the Mg-deficient diet showed some kidney Ca accumulation. The synergistic interaction of fructose and magnesium deficiency on nephrocalcinosis was significantly greater in female than in male rats. Low urinary output, optimal pH 6.8 for calcium phosphate precipitation, hypercalcaemia, hypercalciuria, hypomagnesuria, and low ratio of urinary Mg to Ca may independently or multifactorially contribute to nephrocalcinosis. The possible mechanism of this interaction is discussed.     

Ascorbic acid oral treatment modifies lipolytic response and behavioural activity but not glucocorticoid metabolism in cafeteria diet‐fed rats

Aim: To analyse the effects of vitamin C (VC), a potent dietary antioxidant, oral supplementation on body weight gain, behavioural activity, lipolytic response and glucocorticoid metabolism in the early stages of diet‐induced overweight in rats. Methods: Food intake, locomotive activity and faecal corticosterone were assessed during the 14 day trial period. After 2 weeks, the animals were sacrificed and the body composition, biochemical markers and lipolytic response from isolated adipocytes from retroperitoneal white adipose tissue were examined. Results: The intake of a high‐fat diet by rats induced a significant increase in body weight, adiposity and insulin resistance markers as well as a decrease in faecal corticosterone levels compared with standard diet‐fed rats. Interestingly, the animals fed on the cafeteria diet showed a significant increase in the isoproterenol‐induced lipolytic response in isolated adipocytes. Furthermore, this cafeteria‐fed group showed a reduced locomotive behaviour than the control rats. On the other hand, oral VC supplementation in animals receiving the high‐fat diet restored the cafeteria diet effect in some of the analysed variables such as final body weight and plasma insulin to control group levels. Remarkably, increases in locomotive behaviour and a significant decrease in the lipolytic response induced by isoproterenol on isolated adipocytes from animals treated with VC were observed. Conclusion: This work demonstrates that an oral ascorbic acid supplementation has direct effects on behavioural activity and on adipocyte lipolysis in early obesity stages in rats, which could indicate a protective short‐term role of this vitamin against adiposity induced by chronic high‐fat diet consumption.     

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.     

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.     

Effect of exercise on Hepatic cholesterof of rats fed diets high in saturated or unsaturated fats

Summary Rats have been fed diets containing 24.2% coconut or corn oil or an equal mixture of each for 14–18 weeks. Half of the animals in each dietary group were exercised by running in motor-driven work wheels throughout the entire experimental period. During the final 10–14 weeks, these exercised animals ran continuously for 60 min at 1.0 mph or faster each day. Comparisons between sedentary groups revealed that hepatic cholesterol and excretion of digitonin precipitated sterols in the feces increased (P < 0.01) as the per cent of unsaturated fat (corn oil) in the ingested food increased. In contrast, total liver lipid decreased (P < 0.01) as the consumption of corn oil increased. No change in plasma cholesterol occurred in the sedentary rats in response to the three diets. Hepatic cholesterol of the exercised groups was significantly less (P < 0.05–P < 0.01) than that of their respective control groups (same diet). However, the group fed the corn oil diet had a significantly higher (P < 0.01) liver cholesterol after exercise than did the exercised group fed the coconut oil diet. Liver lipid was reduced (P < 0.01) by exercise in the corn oil and mixed corn-coconut oil fed groups. Plasma cholesterol and sterol excretion were unchanged by the exercise program.This investigation supported by Research Grant HE 08262 from the National Heart Institute, National Institutes of Health, U.S. Public Health Service.     

Effect of pre- and postweaning nutrition on dietary induced obesity in B6D2F2 mice

Our purpose was to ascertain whether a phase of postnatal overfeeding would interact with preweaning litter size in influencing dietary induced obesity in mice. Male and female B6D2F2 mice, reared in small (Sm = 4), medium (Md = 8) and large (Lg = 12) litters were maintained on high fat (HF) or control diets (C) for 6 weeks, beginning at weaning. After a further 4 weeks on lab chow, all animals were fed a cafeteria diet for another 6 week period. Body weight at weaning indicated Lg less than Md and Sm animals. Lg animals gained more weight during the postweaning period but their body weight remained lower than the Sm. HF animals from all litter sizes consumed more calories and gained more weight than C animals. During the period of cafeteria feeding the Sm animals gained more weight than the Md and Lg. Although males were heavier than females, the sexes responded similarly to treatment. The postweaning dietary regimen had no effect on the weight gained in response to cafeteria feeding.