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.     

Effect of a high-fat diet on firing rate of sympathetic nerves innervating brown adipose tissue in anesthetized rats

Three experiments have examined the effects of ad lib and forced intake of a high-fat diet on sympathetic firing rate to brown adipose tissue. Seven days after beginning of ad lib intake of either a low-fat or high-fat diet, sympathetic activity was not significantly different in either group nor was it significantly different from the values obtained in animals measured at the switch from the chow to a semisynthetic high- or low-fat diet. After 22 days on the semisynthetic diet, however, the sympathetic firing rate of animals eating the high-fat diet had decreased nearly 25% and was significantly lower than the animals maintained on the semisynthetic low-fat diet or animals studied at the transition from the chow to the low-fat diet. In a second experiment animals were tube-fed for 3, 6 or 9 weeks on a high- or low-fat diet. Sympathetic firing rate of the rats eating the low-fat diet was higher at all three times, but the difference decreased with longer feeding. To eliminate differences in food intake, animals were tube-fed a moderate- or high-fat liquid diet three times a day for six days. The 80 kcal/day intake produced a steady weight gain in both groups. Liver weight, retroperitoneal white adipose tissue weight, and interscapular brown adipose tissue weight were all significantly greater in the animals fed the high-fat diet. Sympathetic firing rate, however, was significantly lower in the animals fed the high-fat semisynthetic diet as compared to animals fed the moderate-fat diet. These data show the high-fat diets are associated with a reduction in sympathetic activity to brown adipose tissue.     

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 food restriction and adrenalectomy in rats with VMH or PVH lesions

The effects of adrenalectomy in rats with ventromedial or paraventricular hypothalamic lesions have been studied in two experiments. Rats with ventromedial hypothalamic lesions or lesions in the paraventricular nucleus were allowed to gain weight for fourteen days at which time they were adrenalectomized. Before adrenalectomy, animals with VMH lesions ate more, gained significantly more weight than animals with lesions in the paraventricular nucleus, and both were significantly heavier and consumed more food than sham-operated controls. Following adrenalectomy, food intake decreased and both groups of lesioned animals lost weight. The animals with VMH lesions stabilized at weights above the control animals. Implantation of corticosterone enhanced weight gain and food intake in animals with lesions in either the paraventricular nucleus or the ventromedial hypothalamus. In the second experiment, one subgroup of rats with VMH lesions was adrenalectomized, and allowed to eat ad lib. Two other groups of sham-operated rats with VMH lesions served as controls. One group ate ad lib and one group was pair fed to the food intake of the adrenalectomized VMH-lesioned rats. Weight gain in the adrenalectomized VMH-lesioned rats and the pair-fed VMH-lesioned controls was similar and less than the VMH-lesioned rats eating ad lib. GDP binding to interscapular brown adipose tissue was related to the degree of weight gain, not to the presence of the VMH lesion. These data show that corticosterone is essential for the expression of obesity in both PVH- and VMH-lesioned rats. They also argue that the reduction in the activity of the sympathetic nervous system of VMH-lesioned rats as estimated by the GDP binding to mitochondria from brown adipose tissue is associated with hyperphagia.     

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.     

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.     

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 obesity in golden hamsters: Reversibility and effects of sex and photoperiod

Golden hamsters fed a high-fat diet do not overeat, but they become obese because of decreases in energy expenditure. This decrease in actual energy expenditure is accompanied by increases in thermogenic capacity and brown adipose tissue mass, protein content, and DNA content. Three experiments examined this phenomenon in more detail. Experiment 1 demonstrated that this form of dietary obesity is largely reversible simply by returning the animals to a high-carbohydrate chow diet. However, the obesity which develops solely because of decreased energy expenditure is reversed primarily by decreased energy intake. In this respect fat-fed hamsters resemble tube-fed rats. Experiment 2 revealed that the effects of high-fat diet are at least as robust in female hamsters as in males. Experiment 3 examined the interactions between diet and photoperiod. Short days (10 hr light per 24 hr) had almost no effect on male hamsters fed Purina chow. However, nearly all of the effects of the high-fat diet (i.e., increases in body weight gain, feed efficiency, carcass energy content, percent ingested energy stored in the carcass, carcass lipid content, brown adipose tissue protein, and brown adipose tissue DNA) were exaggerated in hamsters housed in short days. High-fat-diet-induced increases in metabolic efficiency and thermogenic capacity may be of value in readying hamsters for winter. Furthermore, as winter approaches, decreasing day length might synergize with changes in diet quality to promote these beneficial changes in energy metabolism. Finally, fat-fed hamsters could be a useful animal model of some kinds of human obesity.     

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.     

Medial hypothalamic lesions in Syrian hamsters: characterization of hyperphagia and weight gain

Syrian golden hamsters (Mesocricetus auratus) received bilateral lesions aimed at the ventromedial hypothalamus (VMH) or a sham lesion. In the first study, some of the animals in each surgical group were housed in standard sedentary conditions while others had free access to running wheels. The lesions produced a 30% increase in the daily intake of chow, and this was accomplished exclusively by increased meal sizes. As a result, lesioned hamsters gained body weight relative to controls both on the chow diet and in a subsequent high fat diet phase. The effects were comparable in both sedentary and exercising groups. The lesions produced increases in body length and fat content. In the second study, lesions were made in the VMH or in adjacent nuclei and, after an initial period on chow, the hamsters were then given a choice between chow and high fat diet. The lesioned hamsters showed no unusual preference for the high fat diet but, as before, those with damage to the VMH or paraventricular nucleus (PVN) showed exaggerated body weight gain. Hamsters with these lesions were hyperinsulinemic in both fed and fasted conditions at the end of the study.     

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.     

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.     

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.     

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.     

Sex differences in the effects of high-fat feeding on behavior and carcass composition

Male and female Sprague-Dawley rats were fed a high-fat diet (40% by weight) for 11 weeks beginning at 70–80 days of age. At the end of the 11th week, high-fat fed rats of both sexes were significantly heavier than chow-fed controls. All rats were then food deprived and were trained to bar-press in an operant chamber for Noyes pellets. Testing on fixed ratio (FR) schedules started when their body weights reached 85% of pre-deprivation levels and they pressed bar steadily. At the end of operant testing, all rats were refed their previous diet until body weights returned to pre-deprivation levels. The animals were then sacrificed. Fat pads from retroperitoneal, inguinal and gonadal regions were dissected out and cellularity determined. Carcass composition was analyzed by chemical methods. On the operant apparatus, the high-fat fed female rats (F-HF) behaved more like VMH lesioned obese rats, i.e. decreased bar pressing responses when compared with controls. No difference in operant responding was found between males fed high-fat diet and chow. Fat cell number and size were increased in retroperitoneal and inguinal fat pad for rats fed high-fat diet. In gonadal pads, only cell size was increased. Females on the high-fat diet had higher percentages of body fat than males on the high-fat diet. The behavioral difference in F-HF rats could be attributed to their higher adiposity. The results support previously reported findings on the behavior and adipose tissue cellularity of dietary obese rats.     

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

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

Influence of noradrenaline on blood flow to brown adipose tissue in rats exhibiting diet-induced thermogenesis

1. The influence of noradrenaline on regional blood flow was determined using radioactive microspheres in rats maintained on either stock diet or a palatable cafeteria diet.
2. Cardiac output and blood flow to brain, lungs, liver and skeletal muscle were similar for rats on the two diets.
3. Blood flow to total dissectable brown adipose tissue in control and cafeteria rats represented 1 and 2% of cardiac output respectively but these values rose to 7 and 15.5% during infusion of noradrenaline.
4. Arterial oxygen content was similar for all groups but the oxygen content of venous blood draining the interscapular brown adipose tissue fell to 6 ml O₂/100 ml blood in control rats and 1 ml/100 ml in cafeteria rats after noradrenaline.
5. The total oxygen consumption of brown adipose tissue was calculated and found to account for 42% of the response to noradrenaline in control rats and 74% in cafeteria animals. The increments in the oxygen consumption of other tissues were almost identical in both groups and so all the diet-induced changes in thermogenic capacity can be attributed to increases in brown adipose tissue metabolism.
6. These findings demonstrate the quantitative importance of brown adipose tissue in diet-induced thermogenesis and confirm the similarities between diet and non-shivering thermogenesis.

     

Suppression of norepinephrine-induced thermogenesis in brown adipose tissue by fasting

Fasting-induced changes in thermogenic responses to norepinephrine (NE, 4.0 micrograms X kg-1 X min-1 iv) were studied in anesthetized rats previously cold acclimated. The rats were divided into five groups at the end of 30-40 days of cold acclimation (5 degrees C). The five groups were kept for 5 days at 25 degrees C and fed (intact fed), fasted (intact fasted), fasted with daily treatment with thyroxine (T4, 2 micrograms/kg sc), thyroidectomized and fed, or thyroidectomized and fasted. In the intact fasted group, in which the weight of brown adipose tissue decreased, NE-induced increases in oxygen consumption, colonic temperature (T col), and temperature of the interscapular brown adipose tissue (TBAT) were markedly suppressed. The two thyroidectomized groups also showed a reduction in thermogenic response. In these three groups, TBAT was lower than Tcol throughout NE infusion. In the T4-treated fasted group, fasting-induced suppression of thermogenic response to NE was largely prevented. In the intact fed and the T4-treated fasted groups, TBAT attained higher values than Tcol during NE infusion. Plasma levels of thyroid hormones were significantly lower in the intact fasted group than in the intact fed or the T4-treated fasted group. These results suggest that fasting-induced suppression of the thermogenic response to NE is largely due to the reduced thermogenic response of brown adipose tissue to NE. The lowering of the levels of the thyroid hormones induced by fasting may be one of a number of causes of the reduction in the thermogenic response of brown adipose tissue.     

Effect of Calorie Restricted Diet on Brown Adipose Tissue in Mice

Calorie restricted diet (50% food intake of control animals) for 3 weeks decelerated weight gain in laboratory mice, reduced the weight of abdominal fat, and decreased the rate of oxygen consumption by brown adipose tissue. The relative weight of interscapular brown fat and protein content in it did not differ from the control. DNA content in brown fat in mice kept on calorie restricted diet increased by 93% compared with the control.