Brown Fat Depots Research Articles

Guanosine diphosphate binding to brown adipose tissue mitochondria is increased after single meal.

A single meal results in an increased thermic activity of brown adipose tissue (BAT). The purpose of the present studies was threefold: 1) to identify major metabolic origins involved in this thermic response, 2) to determine the effect of meal composition on it, and 3) to determine time changes in postprandial brown fat thermogenesis. Wistar rats were trained to eat during 2 feeding sessions/day. On the days of the experiment, rats received a test meal for 2 h, and respective control rats were simultaneously meal deprived. The animals were killed at one or more time points after meal onset, and their BAT was removed for determination of mitochondrial guanosine diphosphate (GDP) binding to indicate rate of uncoupled respiration (expts 1 and 3) or Na+-K+-ATPase activity representing coupled respiration (expt 2). Meal taking was followed by an 85% increase in GDP binding (P less than 0.001). In contrast, Na+-K+-ATPase activity was not altered by a test meal of a similar composition. The largest meal-induced rise in mitochondrial GDP binding was evident during the early postprandial hours, and it was greatly reduced by 10 h after meal onset. Expressed per total interscapular brown fat depot, a high-carbohydrate meal caused a greater increase in GDP binding than an equicaloric high-fat meal. Our data indicate that the BAT proton conductance pathway is activated by a single meal.

Brown adipose tissue lipectomy leads to increased fat deposition in Osborne-Mendel rats.

Inter- and subscapular brown adipose tissue depots were removed from nine female Osborne-Mendel rats. These lipectomized animals and nine sham-operated controls recovered from surgery for 7 days at 25 degrees C and were then placed on a highly palatable liquid diet. All animals were maintained for a 2nd wk at 25 degrees C before being switched to 8 degrees C. After 9 wk in the cold, animals were killed, and the brown adipose tissue was dissected from scapular, cervical, thoracic, perirenal, and axillary regions. Total brown fat pad mass, protein content, brown adipocyte number, citrate synthase activity, and beta-hydroxyacyl CoA dehydrogenase activity in each of the dissected brown fat depots were significantly less than those of the sham-operated controls. Thus there was incomplete metabolic compensation in the remaining brown fat depots after the removal of the scapular brown fat in the lipectomized rats. The mass and lipid content of the retroperitoneal white adipose depot were significantly increased in the lipectomized rats as was their carcass fat content (up 14%). Food intake of the lipectomized rats was slightly but significantly decreased. These data indicate that a reduction in the amount of functional brown fat is accompanied by increased body fat accretion and are thus consistent with the hypothesis that decreased brown adipose thermogenesis can lead to altered energy balance and increased white fat deposition.

Brown adipose tissue in cafeteria-fed hamsters.

Hamsters consuming a "cafeteria diet" had more brown adipose tissue than did chow-fed hamsters. The growth of the brown fat depots in cafeteria-fed hamsters was accompanied by increases in tissue protein and cytochrome oxidase. To assess the thermogenic capacity of brown fat mitochondria, the binding of GDP to isolated mitochondria was measured. Mitochondrial GDP binding was not affected by feeding the cafeteria diet for 4 wk, but more prolonged cafeteria feeding for 8 wk did, however, increase the binding of GDP to isolated mitochondria. The morphology of brown adipose tissue was altered during cafeteria feeding. The brown adipose tissue of cafeteria-fed hamsters had more large unilocular cells than did the brown adipose tissue of chow-fed hamsters. In addition, the average adipocyte diameter was greater in brown adipose tissue of cafeteria-fed hamsters. These data support the presence of a dietary regulation of brown adipose tissue growth in hamsters. The growth of brown adipose tissue in hamsters eating the cafeteria diet appears to result largely from proliferation of adipocytes, as evidenced by the increases in tissue protein and cytochrome oxidase during cafeteria feeding, but some hypertrophy of the adipocytes also occurs. A dietary regulation of brown fat thermogenic capacity is also apparent but this regulation is evident only after more prolonged periods of cafeteria feeding. Hamsters eating a cafeteria diet increase their caloric intake but have the same or greater body weight gain efficiency as do chow-fed animals. The absence of dietary stimulation of thermogenesis may underlie the similar efficiencies of weight gain in chow- and cafeteria-fed hamsters.

CAMP metabolism and lipolysis in brown adipocytes of hamsters consuming a cafeteria diet.

Feeding animals cafeteria diets causes increased sympathetic activity to brown adipose tissue and this is believed to be responsible for the concomitant activation of thermogenesis. Because chronic catecholamine stimulation in other systems leads to a desensitization of beta-adrenergic receptors, we examined lipolysis and cAMP production in brown adipocytes of hamsters eating cafeteria diets for evidence of diminished beta-adrenergic responses. Basal cAMP levels were similar in chow- and cafeteria-fed hamsters. However, adipocytes from overfed animals formed less cAMP in response to isoproterenol than those of control animals. Isoproterenol-stimulated adenylate cyclase activity was similarly decreased in membrane preparations from cafeteria-fed hamsters. However, when the diterpene forskolin was used, equal amounts of cAMP were formed in cells and membrane preparations from control and overfed animals. In contrast to the reduced responses of the cAMP system to isoproterenol stimulation observed in overfed hamsters, isoproterenol-stimulated lipolysis was greater in cells from overfed animals than in cells from control animals. These results are consistent with a desensitization of the adenylate cyclase system in brown adipocytes occurring during chronic hyperphagia. Because eating cafeteria diets has been reported to increase sympathetic activity to brown fat depots, the apparent desensitization of brown adipocytes observed in this study may result from a persistent stimulation of the brown fat with norepinephrine in vivo. Our data also suggest the existence of mechanisms that preserve lipolysis in the face of low cAMP levels.

Lipoprotein lipase activity and cellularity in brown and white adipose tissue in Zucker obese rats

The genetically obese adult Zucker rat (fafa) exhibits reduced thermogenesis when stimulated by physiological agents (cold, catecholamines). Recent evidence suggests that this thermogenic defect may be important in the manifestation of the animal's obesity and that it reflects a reduced thermogenic contribution from brown adipose tissue, the major nonshivering thermogenic site in many mammals. The present study describes the effects of the obese genotype on brown (and white) adipocyte size, number, and lipid content and tissue lipoprotein lipase (LPL) activity. In the obese rats, brown fat depots were increased in mass. This increase could be accounted for by brown fat hypertrophy (due primarily to an increase in the amount of triglyceride present in each cell) rather than hyperplasia (there being no increase in the number of brown fat cells). In addition, unlike the situation in white fat, the brown fat from the obese rats did not exhibit higher LPL activity than did the brown fat from their lean littermates. This absence of an increased capacity for triglyceride uptake, coupled with the greater amount of triglyceride per brown adipocyte, is consistent with a reduction of triglyceride oxidation (and, thus, heat production) in the cells from the obese ( v the lean) rats.

Glycerokinase in mammalian adipose tissue: stimulation by lipogenic substances

A connecting link between carbohydrate and fat metabolism in adipose tissue is theconcentration of alpha-glycerophosphate derived predominantly from the glycolysis ofglucose entering the fat cell. However, several investigators have reported the presence of a glycerol specific kinase in the epidiymal fat-pad of the rat and obob mouse. This enzyme's presence in other mammalian adipose tissue could contribute to the alpha-glycerophosphate pool and thus affect both carbohydrate and fat metabolism within the fat cell. Glycerokinase was demonstrated in isolated fat cells obtained from the subcutaneous, perirenal, epididymal, and dorsal intrascapular brown fat depots of the adultmale rat. It was found to be particularly sensitive to in vivo lipogenic stimuli in both the subcutaneous and the brown adipose tissue and concluded that insulin is involved in adipose glycerokinase stimulation. Therefore, the main function of glycerokinase in normal adipose tissue may be to augment the anabolic action of insulin. It isfurther suggested that deviation from the normal control of this lipogenic enzyme couldlead to a gradual accumulation of fat and eventual obesity.

Effects of cold exposure on tissue blood flow in the new-born lamb.

1. Conscious lambs less than 2 days old were exposed to thermoneutral and to cold environments, and the radioactive microsphere technique was used to obtain measurements of blood flow to most tissues of the body.2. Cold stress was such as to evoke a summit metabolic response. Deep body temperature was within the normal range for thermoneutral conditions, while metabolic rate increased by about 300%, cardiac output by about 30%, and blood pressure by about 25%.3. Blood flow to the thermogenic tissues increased: perirenal, inguinal, pericardial, prescapular and cervical brown fat depots showed a five- to sixfold increase, while the longissimus dorsi, trapezius, gastrocnemius and biceps femoris muscles showed a five- to ninefold increase.4. There was an increase in blood flow in the diaphragm, intercostal, panniculus and cardiac muscles, but a decrease in flow in the skin of the leg, ear and midside, the maxillo turbinals, thyroids, spleen, kidneys, liver and gut. There were no significant changes in total or regional blood flow in the brain or spinal cord, or in the adrenals, nasal mucosa or tongue.5. Results support other evidence that thermogenesis in both brown fat and skeletal muscle is very important in the new-born lamb exposed to cold. Changes in flow in other tissues correlated with known functions in the cold animal. The redistribution of cardiac output during cold stress is a further example of circulatory adjustments which enable animals to cope with stress states.6. Many differences between blood flow values obtained by the radio-active microsphere and other techniques for measuring blood flow are noted and discussed.

Comparison of brown fat metabolism in cold-exposed rats and golden hamsters.

LIPID metabolic pathways are important in cold acclimation of mammals and in mammalian hibernation, both during preparation for it and in the actual hibernating state. The brown fat depots found in all hibernating and some non-hibernating mammalian species have been extensively studied from what may be termed an analytical approach. The metabolism of these depots has also been investigated. The importance of brown fat to the hibernating mammal is generally accepted, but its actual role in the hibernating phenomenon is still problematical. Our recent investigations concern metabolic changes in brown fat during the process of cold acclimation in both a hibernating and a non-hibernating mammal. The tissue could participate in this process as a thermogenic organ. This has been suggested by Smith and Hoch1 for one species of hibernating mammal.

ACETATE-1-C14 UTILIZATION BY BROWN FAT FROM HAMSTERS IN COLD EXPOSURE AND HIBERNATION.

The in vitro conversion of acetate-1-C14to C14O2and C14-lipid by the interscapular and cervical brown fat depots of cold-exposed golden hamsters was measured. Tissue samples were taken from animals after 48 hours, 3 weeks, and 6–8 weeks in the cold, in hibernation, and arousing from hibernation and immediately after arousal. There was a depression in C14O2production by cervical tissue after 48 hours in the cold, and by interscapular tissue after 3 weeks in the cold. C14O2production by both depots remained low throughout acclimation, hibernation, and arousal. C14-Lipid production by both depots increased after 48 hours in the cold and remained high during acclimation. C14-Lipid production was depressed during hibernation and arousal, with recovery to acclimated levels at the end of arousal in the interscapular, but not in the cervical depot. Cervical brown fat had a higher conversion to both C14O2and C14-lipid than interscapular brown fat. Qualitatively, but not quantitatively, brown fat behaved similarly to white fat. It was concluded that increased lipogenic capacity is not a primary response of brown fat to cold exposure of the animal, but that some other pathway becomes highly active.