guanosine-diphosphate and Body-Weight

To investigate the effects of prolonged dietary sodium restriction on lipid metabolism, male rats weighing 35 to 40 g (just weaned) were fed either a low-salt (LSD) or a normal salt diet (NSD) and used in metabolic experiments after 1, 2, or 3 months of diet consumption. After 2 and 3 months on the diet, LSD rats showed increased amounts of lipid in carcass and retroperitoneal tissue. In both LSD and NSD, extending the feeding period from 2 to 3 months resulted in a marked reduction in the in vivo rates of adipose tissue fatty acid synthesis that was accompanied by increases in liver lipogenesis and in the activity of adipose tissue lipoprotein lipase (LPL). However, these increases were more marked in LSD rats. Thus, in vivo rates of liver fatty synthesis and LPL activity in LSD rats, which were already higher (by about 35% and 20%, respectively) than in controls after 2 months, attained levels 50% higher than those in NSD animals after another month on the diet. Brown adipose tissue (BAT) thermogenic capacity, estimated after 2 and 3 months by the tissue temperature response to norepinephrine (NE) injection and by guanosine diphosphate (GDP) binding to BAT mitochondria, did not change in controls, but was significantly reduced in LSD rats. This raises the possibility that a decrease in overall energy expenditure, together with an LPL-induced increased uptake of preformed fatty acids from the circulation, may account for the excessive lipid accumulation in LSD rats. Taken together, the data indicate that prolonged dietary sodium restriction exacerbates normal, age-related changes in white and BAT metabolism.

Topics: Adipose Tissue; Adipose Tissue, Brown; Aging; Animals; Body Temperature Regulation; Body Weight; Diet, Sodium-Restricted; Eating; Fatty Acids; Glycerol; Guanosine Diphosphate; Lipids; Lipoprotein Lipase; Liver; Male; Mitochondria; Norepinephrine; Rats; Rats, Wistar; Triglycerides; Vasoconstrictor Agents

Repeat immobilization-stressed rats are leaner and have improved cold tolerance due to enhancement of brown adipose tissue (BAT) thermogenesis. This process likely involves stress-induced sympathetic nervous system activation and adrenocortical hormone release, which dynamically enhances and suppresses uncoupling protein 1 (UCP1) function, respectively. To investigate whether repeated immobilization influences UCP1 thermogenic properties, we assessed UCP1 mRNA, protein expression, and activity (GDP binding) in BAT from immobilization-naive or repeatedly immobilized rats (3 h daily for 4 weeks) and sham operated or adrenalectomized (ADX) rats. UCP1 properties were assessed before (basal) and after exposure to 3 h of acute immobilization. Basal levels of GDP binding and UCP1 expression was significantly increased (140 and 140%) in the repeated immobilized group. Acute immobilization increased GDP binding in both naive (180%) and repeated immobilized groups (220%) without changing UCP1 expression. In ADX rats, basal GDP binding and UCP1 gene expression significantly increased (140 and 110%), and acute immobilization induced further increase. These data demonstrate that repeated immobilization resulted in enhanced UCP1 function, suggesting that enhanced BAT thermogenesis contributes to lower body weight gain through excess energy loss and an improved ability to maintain body temperature during cold exposure.

Topics: Adipose Tissue, Brown; Adrenalectomy; Animals; Body Temperature; Body Weight; Carrier Proteins; Corticosterone; Eating; Guanosine Diphosphate; Immobilization; Ion Channels; Male; Membrane Proteins; Mitochondria; Mitochondrial Proteins; Rats; Rats, Wistar; Recurrence; Stress, Physiological; Uncoupling Protein 1

We investigated the relative importance of overeating, thermogenesis, and uncoupling protein (UCP) expression in determining the severity of obesity in male Wistar rats fed a highly palatable diet. After 2 wk of feeding, body weight did not differ significantly from controls (248 +/- 4 vs. 229 +/- 3 g; P > 0.3), but rectal temperature, brown adipose tissue (BAT) mass, UCP3 expression in gastrocnemius muscle, and UCP2 expression in white adipose tissue (WAT) were all elevated in diet-fed animals. In a further study, rats fed a palatable diet for 8 wk exhibited higher energy intake and rectal temperature than controls. Dietary-obese rats were divided into high (427-490 g; n = 8) and low (313-410 g; n = 10) weight gainers. The high gainers ate significantly more than the low gainers, and energy intake was positively correlated with weight gain (r(2) = 0.72, P < 0.01). UCP2 and UCP3 mRNA levels in gastrocnemius muscle were significantly increased above lean controls in all diet-fed animals, whereas UCPs in WAT and BAT did not differ significantly from controls. Whereas rats fed palatable food exhibited a thermogenic response, there was no significant difference in core temperature between high and low gain groups (37. 5 +/- 0.1 vs. 37.6 +/- 0.1 degrees C; P > 0.5). We conclude that a higher energy intake is the critical factor determining susceptibility to dietary obesity in unselected Wistar rats.

Topics: Adipose Tissue, Brown; Animals; Body Composition; Body Temperature; Body Weight; Carrier Proteins; Diet; Energy Intake; Energy Metabolism; Fatty Acids, Nonesterified; Guanosine Diphosphate; Hyperphagia; Insulin; Ion Channels; Leptin; Male; Membrane Proteins; Membrane Transport Proteins; Mitochondria; Mitochondrial Proteins; Muscle, Skeletal; Obesity; Protein Biosynthesis; Rats; Rats, Wistar; Triglycerides; Uncoupling Protein 1; Uncoupling Protein 2; Uncoupling Protein 3

Brown adipose tissue (BAT), a highly thermogenic tissue in young animals, is relatively atrophied and thermogenetically quiescent (e.g. as measured by colonic temperature) in mice that are obese or old. The aim of the current study was to investigate the effect of aging (3.1 (young) versus 14.6 (old) months old) on BAT activity in lean and obese (ob/ob) mice. In young but not in old mice, BAT mass in terms of weight per unit body weight was significantly lower in obese mice than in lean mice. A significant increase in BAT mass of obese mice with age was noted in terms of weight or weight per unit body weight, probably because of a tendency to become white adipose tissue and the deposit of fat, accompanied by the lowest levels of total protein, guanosine 5'-diphosphate binding, and uncoupling protein (UCP) antigen in the mitochondria of BAT, as well as the lowest colonic temperature among the groups examined. Unlike old lean animals, the old obese (ob/ob) animals did not increase but rather decreased the expression of mRNA for UCP in the mitochondria of BAT. These findings suggest that a marked decrease in BAT thermogenic capacity and activity is noted in old obese mice, probably due to synergism of aging and obesity.

Topics: Adipose Tissue, Brown; Aging; Animals; Body Weight; Guanosine Diphosphate; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Proteins; RNA, Messenger

The effects of acute and chronic acclimation to cold on uncoupling protein 1 (UCP1) levels, as well as on GDP-binding to mitochondria, cytochrome c oxidase activity and mitochondrial protein concentration in brown adipose tissue (BAT) of intact male and female rats have been analyzed. Results reveal that females rats are more sensitive to cold because their threshold temperature for the thermogenic response is set at a higher value (around 22 degreesC) than that of males (around 18 degreesC), hence leading to differences in BAT UCP1 levels between the sexes at different environmental temperatures. In vitro experiments showed that steroid hormones, beta-estradiol, estrone and progesterone, can reduce norepinephrine-induced UCP1 synthesis in brown adipocytes differentiated in primary culture. Thus the different sex-associated response of cold-induced thermogenesis in rats does not appear to be explained by a direct action of sex steroids upon the adipocyte, implying that other factors in the thermogenic regulatory system must be involved.

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Carrier Proteins; Cells, Cultured; Cold Temperature; Environmental Exposure; Estradiol; Estrone; Female; Guanosine Diphosphate; Ion Channels; Male; Membrane Proteins; Mice; Mitochondria; Mitochondrial Proteins; Norepinephrine; Progesterone; Rats; RNA, Messenger; Sex Factors; Temperature; Uncoupling Agents; Uncoupling Protein 1

We have previously shown that feeding 50 ml of colostrum can increase the thermogenic activity of brown adipose tissue (BAT) in newborn lambs maintained at a warm (30 degrees C) ambient temperature. This study further examines the effect of ambient temperature on BAT and thermoregulation by investigating the response to feeding 50 ml of water. Immediately after vaginal birth, lambs were placed in either a warm (30 degrees C) or cool (15 degrees C) environment a ambient temperature and measurements of colonic temperature and heat production were recorded for 6 h. Lambs were fed 50 ml of water when 5 h old. The level of guanosine 5'-diphosphate (GDP) binding was higher, but adrenaline content lower in BAT sampled from lambs maintained at 15 degrees C compared with those at 30 degrees C. Feeding was associated with an increase in colonic temperature and plasma concentrations of glucose and non-esterified fatty acids in lambs maintained at 15 degrees C only. In this group plasma concentrations of adrenaline and dopamine declined after feeding, but noradrenaline concentrations were not influenced by feeding in either group of lambs. O2 consumption and CO2 production were higher in lambs maintained at 15 degrees C but were not influenced by ambient temperature or feeding. It is concluded that feeding a small volume of water can influence thermoregulation by a mechanism that is dependent on the ambient temperature at which the lamb is maintained.

Topics: Adipose Tissue, Brown; Animals; Animals, Newborn; Blood Glucose; Body Temperature Regulation; Body Weight; Catecholamines; Colon; Drinking; Fatty Acids, Nonesterified; Guanosine Diphosphate; Intestinal Absorption; Mitochondria; Oxygen Consumption; Proteins; Sheep; Temperature

Brown adipose tissue (BAT) of obese animals is generally in a relatively atrophied and thermogenically quiescent state. The aim of the current study was to investigate the effect of swimming training on BAT activity in lean and obese (ob/ob) mice. The trained mice underwent a 6-week endurance swimming training (1 h/day, 5 days/week) in water at 35-36 degrees C. The swimming training significantly increased BAT mass and its protein content in both the lean and obese mice, suggesting hypertrophy. After swimming training, the amounts of protein and guanosine 5'-diphosphate binding in the mitochondria recovered from BAT of both mice increased significantly as compared with the respective sedentary groups, whereas the uncoupling protein (UCP) content increased significantly only in lean mice. After swimming training, the level of UCP mRNA expression did not change substantially in lean mice but appeared to increase in obese mice. The results obtained here suggest that swimming training leads to an increase in the nonshivering thermogenesis of obese mice in addition to lean mice.

Topics: Adipose Tissue, Brown; Animals; Blotting, Northern; Blotting, Western; Body Weight; Carrier Proteins; Gene Expression Regulation; Guanosine Diphosphate; Ion Channels; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mitochondrial Proteins; Obesity; Organ Size; Protein Binding; Rats; RNA, Messenger; Uncoupling Protein 1

The presence of brown adipose tissue (BAT) in marsupials is controversial because attempts to identify mitochondrial uncoupling protein (UCP) have been unsuccessful. Sminthopsis crassicaudata is a small nocturnal marsupial with an interscapular pad of adipose tissue. Electron microscopy revealed this tissue to have characteristics typical of BAT. GDP binding and UCP detection by immunoblot confirmed BAT. Expression of UCP was increased by cold exposure. When animals were placed from 28 to 15 degrees C, body temperature (Tb) decreased by 1.7 degrees C within 30 min and a further 1.0 degree C by 90 min (P < 0.001) before stabilizing at these lower levels. When animals were returned to 28 degrees C, Tb increased within 30 min (P < 0.001) and returned to basal by 120 min. When animals were maintained at 15 degrees C with ad libitum food for 12 days, Tb (P < 0.05), tail width (P < 0.04), and O2 consumption (P < 0.01) all decreased. The respiratory quotient increased (P < 0.001), indicating a change from fat to carbohydrate utilization. Food intake was unchanged, and body weight increased on day 1 (P < 0.01) before returning to baseline on day 3, remaining stable thereafter. These data suggest that although BAT is present in the marsupial S. crassicaudata, it may not be necessary for thermogenesis, at least in the short term. S. crassicaudata utilizes a plasticity in Tb and a change in substrate utilization to maintain energy balance and body composition without the need for an increase in metabolic rate or food consumption and without the need for torpor.

Topics: Acclimatization; Adipocytes; Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Carrier Proteins; Cold Temperature; Energy Metabolism; Feeding Behavior; Guanosine Diphosphate; Ion Channels; Male; Marsupialia; Membrane Proteins; Mice; Microscopy, Electron; Mitochondria; Mitochondrial Proteins; Models, Biological; Oxygen Consumption; Uncoupling Protein 1

The aim of the present work is to investigate the effect of starvation on brown adipose tissue thermogenic activity with aging. Interscapular brown adipose tissue from female Wistar rats of different ages was used; half of them were fed and the other half were starved for 24 hours. Mitochondria were isolated and mitochondrial protein content, GDP-binding, Cytochrome-c Oxidase activity and uncoupling protein levels were measured. Results show a decrease of all studied parameters, indicating a diminished thermogenic activity with age. The response to starvation is almost the same in all the parameters studied: a general reduction with starvation and a progressive disappearance of this response to starvation with aging. On the whole, these results would indicate a deficient regulation of brown adipose tissue thermogenic activity in old animals, as it happens in other animal models with an alterated thermogenesis.

Topics: Adipose Tissue; Adipose Tissue, Brown; Age Factors; Animals; Body Temperature Regulation; Body Weight; Electron Transport Complex IV; Female; Food Deprivation; Guanosine Diphosphate; Mitochondria; Organ Size; Proteins; Rats; Rats, Wistar; Starvation

To study the responses of thermogenic activity in brown adipose tissue (BAT) to unloading, male Wistar rats were hindlimb suspended for 10 days. Compared with control rats, a significant increase in the BAT-to-body mass ratio and considerable differences in chemical components in BAT were observed in the hindlimb-suspended rats. These findings indicate a marked increase in the thermogenic capacity in BAT of the experimental group. Likewise, the thermogenic activity (which was assessed by guanosine 5'-diphosphate binding to BAT mitochondria) was markedly greater in the mitochondria recovered from BAT of the hindlimb-suspended rats than in those from the control rats (1,610 +/- 450 vs. 202 +/- 132 pmol recovered). Moreover, the uncoupling protein content in the BAT mitochondrial fraction of the hindlimb-suspended rats was significantly higher (1.6-fold) than that in the control rats. As was expected, the uncoupling protein mRNA expression was greater in hindlimb-suspended rats than in control animals. These results suggest that chronic hindlimb suspension leads to an increase in both the thermogenic capacity and the activity in BAT of rats.

Topics: Adipose Tissue, Brown; Animals; Blotting, Western; Body Temperature Regulation; Body Weight; Carrier Proteins; DNA; Electrophoresis, Polyacrylamide Gel; Guanosine Diphosphate; Ion Channels; Male; Membrane Proteins; Mitochondria; Mitochondrial Proteins; Oligonucleotide Probes; Proteins; Rats; Rats, Wistar; RNA; Uncoupling Protein 1; Weightlessness; Weightlessness Simulation

Brown adipose tissue (BAT) contains glucocorticoid receptors; glucocorticoids are required for maintaining differentiated BAT in culture. These studies were performed to determine the effects of corticosterone on BAT thermogenic function and lipid storage. Rats were adrenalectomized and given subcutaneous corticosterone pellets in concentrations that maintained plasma corticosterone constant across the range of 0-20 micrograms/dl or were sham adrenalectomized. All variables were examined 5 days after surgery and corticosterone replacement. Measures of BAT function-thermogenic capacity [guanosine 5'-diphosphate (GDP) binding and uncoupling protein (UCP; a BAT-specific thermogenic protein)] and storage (BAT wet wt, protein, and DNA levels) were made. Plasma hormones (corticosterone, adrenocorticotropic hormone, insulin, 3,3',5-triiodothyronine, and thyroxine were measured. Corticosterone significantly affected BAT thermogenic measures: UCP content and binding of GDP to BAT mitochondria decreased with increasing corticosterone; GDP binding characteristics in BAT from similarly prepared rats examined by Scatchard analysis showed that maximum binding (Bmax) and dissociation constant (Kd) decreased with increasing corticosterone dose. BAT DNA was increased by adrenalectomy and maintained at intact levels with all doses of corticosterone; BAT lipid storage increased dramatically at corticosterone values higher than the daily mean level in intact rats. Histologically, the number and size of lipid droplets within BAT adipocytes increased markedly with increased corticosterone. White adipose depots were more sensitive to circulating corticosterone concentrations than were BAT depots and increased in weight at levels of corticosterone that were at or below the daily mean level of intact rats. We conclude that, within its diurnal range of concentration corticosterone acts to inhibit nonshivering thermogenesis and increase lipid storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipocytes; Adipose Tissue; Adipose Tissue, Brown; Adrenalectomy; Adrenocorticotropic Hormone; Animals; Body Temperature Regulation; Body Weight; Carrier Proteins; Corticosterone; DNA; Dose-Response Relationship, Drug; Drug Implants; Epididymis; Glycogen; Guanosine Diphosphate; In Vitro Techniques; Insulin; Ion Channels; Lipid Metabolism; Male; Membrane Proteins; Mitochondrial Proteins; Pituitary Gland, Anterior; Rats; Rats, Sprague-Dawley; Thyroxine; Time Factors; Triiodothyronine; Uncoupling Protein 1

Despite anorexia, cancer development is frequently accompanied by an increase of energy expenditure. Considering the pivotal role played by brown adipose tissue (BAT) in the energy metabolism of small mammals, we investigated the functional and compositional modification in BAT of anorexic tumor-bearing (Yoshida sarcoma) and pair-fed control rats. BAT thermogenic activity (assessed by maximal mitochondrial GDP binding) was 1.8-fold greater in tumor-bearing rats than in controls, while the thermogenic capacity (assessed by measurement of uncoupling protein) was unchanged. This suggests that tumor bearing had induced an unmasking of uncoupling protein sites. BAT hypertrophy and hyperplasia, characteristic of full-fledged BAT activation, did not occur. The mitochondrial oxidative capacity of BAT (assessed by cytochrome c oxidase activity) was 1.6-fold lower in tumor-bearing than in control rats. The main compositional modification observed in BAT of tumor-bearing rats was an increase in the saturation of cardiolipin fatty acids. These results suggest that the BAT stimulation induced by tumor bearing after 10 days is almost exclusively functional and that the tissue development is limited, probably by anorexia. However, a suppressive effect of anorexia inhibition by tumor bearing cannot be excluded.

Topics: Adipose Tissue, Brown; Animals; Anorexia; Body Temperature Regulation; Body Weight; Cachexia; Cardiolipins; Eating; Electron Transport Complex IV; Fatty Acids; Guanosine Diphosphate; In Vitro Techniques; Male; Mitochondria; Rats; Rats, Wistar; Sarcoma, Yoshida; Uncoupling Agents

Experiments were designed to investigate the involvement of brown adipose tissue (BAT) thermogenesis in the weight loss exhibited by Djungarian hamsters (Phodopus sungorus campbelli) in response to a short photoperiod. Significant decreases in body weight preceded reductions in food intake, suggesting a photoperiod-induced change in energy expenditure. Sixteen weeks exposure to short photoperiod resulted in large decreases in body weight and interscapular BAT mass that were accompanied by an increase in the thermogenic activity of BAT (estimated by mitochondrial GDP binding). However, exposure to short photoperiod for 8 weeks, that induced smaller but significant reductions in body weight, was without effect on the BAT parameters measured. This suggests that increased BAT thermogenesis is unlikely to initiate, or contribute to, the early stages of photoperiod-induced weight loss. In addition, short photoperiod failed to induce any change in the specific activity or sensitivity of adenylate cyclase in BAT membranes, in contrast to the downregulation of catecholamine-stimulated cAMP production observed in BAT following cold exposure.

Topics: Adenylyl Cyclases; Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Carrier Proteins; Circadian Rhythm; Cricetinae; Eating; Guanosine Diphosphate; Ion Channels; Light; Male; Membrane Proteins; Mitochondria; Mitochondrial Proteins; Phodopus; Uncoupling Protein 1

We examined the effect of delivering near-term twin lambs by cesarean section into a warm (30 degrees C) or cool (15 degrees C) ambient temperature on the control of thermoregulation. Heat production was measured 20-30 h after birth during non-rapid-eye-movement sleep at 29 and 14 degrees C. At 29 degrees C there was no difference in heat production between groups, but at 14 degrees C cool-delivered (CD) lambs exhibited a 62% greater metabolic response. Irrespective of delivery temperature, 15 of the 18 lambs used shivering thermogenesis during cold exposure, indicating a reduction in the ability to use nonshivering thermogenesis in brown adipose tissue (BAT). Mean plasma concentrations of thyroxine and triiodothyronine were 35 and 45% greater, respectively, in CD lambs than in warm-delivered lambs. The level of guanosine 5'-diphosphate binding in BAT was lower than in normally delivered lambs and was not different between CD and warm-delivered lambs. Cesarean section delivery prevents the rise in BAT thermogenic activity, which results in an increased reliance on shivering thermogenesis to maintain colonic temperature. Under these conditions, delivery into a cool environment increases the plasma concentration of thyroid hormones, which benefits the neonate by enabling a greater thermogenic response via shivering.

Topics: Adipose Tissue, Brown; Animals; Animals, Newborn; Body Temperature Regulation; Body Weight; Carbon Dioxide; Cesarean Section; Diet; Female; Guanosine Diphosphate; Iodide Peroxidase; Mitochondria; Oxygen Consumption; Pregnancy; Sheep; Shivering; Sleep; Temperature; Thyroid Hormones

Brown adipose tissue (BAT) thermogenesis is an uncoupled ATPase-independent thermogenic mechanism. Ion transport by the Na,K pump is an ATPase-dependent thermogenic mechanism. Both have been proposed as mechanisms of altered energy expenditure during states of dietary energy surfeit and deficit. Our aim was to study these mechanisms during diet-induced obesity and weight loss. Over 36 weeks rats were fed lard- or tallow-based diets (63% energy as fat), or a control diet (12% energy as fat). During periods of restriction rats were fed 50% of the energy intake of controls in the form of a control diet. Several components of thermogenic response increased in rats eating high fat diets and decreased following dietary restriction. BAT activation occurred, particularly with a lard-based diet, as indicated by increased GDP binding and uncoupling protein (UCP) content. Na,K pump activity in thymocytes increased with the feeding of both high fat diets at some time points. Plasma T3 level increased in rats eating the lard-based diet and decreased with dietary restriction regardless of previous diet. Resting metabolic rate (RMR) of the animals was unchanged despite increases in these thermogenic components and was decreased in all groups following dietary restriction. Our results indicate a lack of any major role for activated BAT thermogenesis in mitigating the extent of the obesity induced by the high fat diets. The reasons for the differences in response to the two different sources of saturated fat, lard, and tallow, are not clear.

Topics: Adenosine Triphosphatases; Adipose Tissue; Adipose Tissue, Brown; Animals; Body Composition; Body Weight; Carrier Proteins; Diet; Energy Intake; Energy Metabolism; Guanosine Diphosphate; Ion Channels; Male; Membrane Proteins; Mitochondrial Proteins; Obesity; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase; Thermogenesis; Thymus Gland; Thyroxine; Time Factors; Triiodothyronine; Uncoupling Protein 1; Weight Loss

The effect of lactation on brown adipose tissue (BAT) thermogenic activity and capacity as well as on uncoupling protein (UCP) gene expression has been studied in the 13-lined ground squirrel. Lactating animals were studied after approximately 21 days of lactation. Parameters of thermogenesis were also studied in a group of postpregnant animals from which litters had been removed at 1-2 days postpartum. A group of animals that did not bear litters served as nonpregnant controls. BAT pad weights, protein concentration, and mitochondrial mass were all significantly decreased relative to nonpregnant controls and postpregnant animals. Specific binding of GDP and total GDP bound were significantly decreased in lactating animals relative to both nonpregnant and postpregnant animals. Scatchard analysis of GDP binding indicated that binding affinity (Kd) was unaffected by treatment. UCP concentrations were reduced by 26% during lactation, whereas total UCP content was reduced by 70%. A 3-wk period after pup removal was sufficient for UCP concentrations to return to nonpregnant levels, although total UCP content remained reduced. The changes in UCP concentrations were accompanied by parallel alterations of gene expression. UCP mRNA-to-beta-actin mRNA ratios during lactation were 30% of the levels found in nonpregnant controls and postpregnant animals. The results presented here clearly indicate that BAT activity and capacity are suppressed during lactation in the 13-lined ground squirrel.

Topics: Adipose Tissue, Brown; Animals; Blotting, Northern; Body Temperature Regulation; Body Weight; Carrier Proteins; Electron Transport Complex IV; Female; Guanosine Diphosphate; Ion Channels; Lactation; Membrane Proteins; Mitochondrial Proteins; Organ Size; RNA, Messenger; Sciuridae; Uncoupling Protein 1

The functional state of interscapular brown adipose tissue (IBAT) was examined in rats fed for 20-30 d a high protein, carbohydrate-free diet [70% (wt/wt) protein, 8% fat] or a balanced diet (66% carbohydrate, 17% protein, 8% fat). In rats fed the high protein diet, body weight did not differ from that of control rats, but relative IBAT weight (grams per 100 g body wt) and lipid concentration (per gram of tissue) were 37% and 14% lower, respectively. In vivo rates of lipogenesis in IBAT, epididymal and retroperitoneal adipose tissue of rats fed the high protein diet were 20, 30 and 40%, respectively, of control values. Mitochondrial protein and cytochrome oxidase activity per total IBAT were significantly lower in rats fed the high protein diet than in controls; GDP binding was lower even when expressed per total tissue or per milligram of mitochondrial protein. The increase of IBAT temperature following norepinephrine infusion was significantly smaller than in controls. It is suggested that the decrease in IBAT capacity in the rats fed the high protein diet was due, at least in part, to a sustained reduction of sympathetic activity.

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Dietary Carbohydrates; Dietary Proteins; Electron Transport Complex IV; Fatty Acids; Guanosine Diphosphate; Lipids; Male; Mitochondria; Norepinephrine; Organ Size; Proteins; Rats

1. This study examines the effect of chronic cold exposure during pregnancy, induced by winter shearing twin-bearing ewes 4 weeks before predicted lambing date, on O2 consumption and CO2 production during non-rapid-eye-movement (REM) sleep in lambs maintained for at least 1 h at warm (28-18 degrees C) and cold (14-5 degrees C) ambient temperatures at 1, 4, 14 and 30 days of age. This was combined with measurement of the thermogenic activity (GDP binding to uncoupling protein in mitochondrial preparations) of perirenal adipose tissue from lambs immediately after birth and at 33 days of age. 2. Lambs born from shorn (cold-exposed) ewes were 15% heavier (P < 0.01) and possessed 21% (P < 0.01) more perirenal adipose tissue that contained 40% more protein and mitochondrial protein than unshorn (P < 0.05) controls. Total GDP binding in perirenal adipose tissue was 40% greater (P < 0.05) in lambs born from shorn ewes but there was no difference in lipid content of this tissue between the two groups. 3. At 1 day of age, lambs born from shorn ewes exhibited a 16% higher (P < 0.05) rate of O2 consumption (per kilogram bodyweight) at the warm temperature and a 40% greater metabolic response to the cold ambient temperature. All lambs born from shorn ewes responded to cold exposure without shivering (i.e. via non-shivering thermogenesis) whilst shivering was measured in four out of seven lambs in the unshorn group. These differences had disappeared by 4 days of age as a result of a 25% increased (P < 0.01) rate of O2 consumption in the warm in lambs born from unshorn ewes and a 20% decrease (P < 0.05) in the response to the cold in lambs from shorn ewes. Shivering during cold exposure was measured in six out of nine lambs born from shorn ewes indicating a rapid alteration in thermoregulatory responses to cold during the first few days of life. 4. The levels of GDP binding and mitochondrial protein in perirenal adipose tissue fell by one-third in both groups of lambs during the first 33 days of life whereas lipid content either increased or was unchanged. This indicated that brown adipose tissue (BAT) was developing the characteristics of white adipose tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adipose Tissue; Animals; Animals, Newborn; Body Temperature; Body Temperature Regulation; Body Weight; Cold Temperature; Female; Guanosine Diphosphate; Oxygen Consumption; Pregnancy; Prenatal Exposure Delayed Effects; Sheep

Brown adipose tissue (Na(+)-K+)-ATPase activity, in vitro glucose uptake and 2-aminoisobutyric acid uptake, as well as mitochondrial GDP-binding and succinate dehydrogenase activity were determined in order to study the relationship between these parameters in control, cold acclimated and cafeteria-fed rats. GDP-binding, (Na(+)-K+)-ATPase and glucose uptake were increased in interscapular brown adipose tissue from cold-acclimated and cafeteria-fed rats, whereas 2-aminoisobutyric acid uptake was only increased in cafeteria-fed rats. GDP-binding and (Na(+)-K+)-ATPase activity showed a high correlation coefficient suggesting a parallel modulation of both systems, which would probably share a common regulation mechanism.

Topics: Adipose Tissue, Brown; Aminoisobutyric Acids; Animals; Body Temperature Regulation; Body Weight; Cold Temperature; Female; Glucose; Guanosine Diphosphate; Insulin; Mitochondria; Rats; Rats, Inbred Strains; Sodium-Potassium-Exchanging ATPase; Succinate Dehydrogenase

1. The thermogenic activity of brown adipose tissue in hibernating garden dormice during hypothermic torpor and at different states of arousal were studied. High levels of GDP binding were observed on isolated brown fat mitochondria, indicating that the thermogenic proton conductance pathway is very active in brown fat during arousal. 2. In order to investigate this phenomenon, the uncoupling protein was assessed by immunological assay and the mRNA for UCP was analysed. 3. Animals during arousal exhibited neither increase in UCPmRNA nor an increase in UCP. 4. Our results suggest that during the rewarming of garden dormice there is an acute unmasking of GDP binding sites on the protein.

Topics: Adipose Tissue, Brown; Animals; Arousal; Blotting, Northern; Body Temperature Regulation; Body Weight; Guanosine Diphosphate; Hibernation; Immunoblotting; Mitochondria; Protein Binding; Rodentia

Resting oxygen consumption (VO2) and mitochondrial GDP binding were measured in hypothyroid and euthyroid rats after administration of selective and nonselective beta-adrenoceptor agonists (BRL 35135A and Isoprenaline--BRL, ISO). Resting VO2, VO2 increment and mitochondrial GDP binding after beta-agonists were lower in hypothyroid rats than in the euthyroid group. The reduced response was more marked for ISO than for BRL. These results suggest that BRL is acting on a beta-adrenoceptor which differs from beta-1 and beta-2 adrenoceptors, responsible for the effect of ISO. Activation of thermogenesis via this beta-3 adrenoceptor seems to be less dependent on permissive levels of thyroid hormones than on activation via beta-1 and/or beta-2 adrenoceptors.

Topics: Adipose Tissue; Adrenergic beta-Agonists; Animals; Body Weight; Disease Models, Animal; Guanosine Diphosphate; Hypothyroidism; Isoproterenol; Male; Methimazole; Oxygen Consumption; Phenethylamines; Rats; Rats, Sprague-Dawley; Thermoreceptors; Thyroidectomy

Although the rat is usually not considered to be sensitive to photoperiod, under some experimental conditions photoperiod responses are unmasked. In addition, we have observed photoperiod-induced changes in body weight gain in lean and obese Zucker rats. In this experiment, body mass, food intake, body composition, brown adipose tissue (BAT) thermogenic state, and blood concentrations of corticosterone, insulin, and glucose were evaluated under one of two lighting conditions: a short (10 h light: 14 h dark) or a long (14 h light: 10 h dark) photoperiod. Plasma corticosterone and glucose concentrations measured under fasting conditions were unaffected by photoperiod in either genotype. The amount of BAT mitochondrial protein isolated was less in long photoperiod rats. BAT mitochondrial GDP binding was unaffected by photoperiod in the lean rats, but tended to be lower in long photoperiod obese rats than in short photoperiod obese rats. Although, photoperiod had no effect on daily food intake of rats exposed to the short versus long photoperiod, body mass was heaviest in obese rats raised in long photoperiod. Plasma insulin was increased in both lean and obese rats in long photoperiod. In addition, fat storage appeared to shift to internal depots in the lean rats exposed to long photoperiod. Our data demonstrate that photoperiod does have an effect on male Zucker rats with respect to body weight and fat distribution, with the obese rats being more sensitive to changes in photoperiod than the lean rats.

Topics: Adipose Tissue, Brown; Animals; Blood Glucose; Body Weight; Corticosterone; Energy Intake; Guanosine Diphosphate; Insulin; Light; Male; Mitochondria; Rats; Rats, Zucker; Weight Gain

Our aims were to further characterize the stimulatory effect of glucagon on brown fat and to test the hypothesis that physiological levels of hyperglucagonemia would stimulate brown fat thermogenesis. In the first set of experiments, glucagon (1 mg/kg sc twice daily) or vehicle control was administered three times in 26 h. This large dose of glucagon produced increases in GDP binding to brown fat mitochondria. In addition, Scatchard analysis indicated a glucagon-induced increase in number of GDP binding sites without evidence for alteration in binding site affinity. No consistent increase in brown fat mitochondrial GDP binding was produced 2 h after a single injection of glucagon (1 mg/kg). In the second set of experiments, glucagon was administered intraperitoneally by constant osmotic minipump infusion. Glucagon in a dose of 150 micrograms.kg-1.day-1 for 5 days produced significant increases in GDP binding to brown fat mitochondria, whereas glucagon serum levels were increased but stayed within the usual physiological range. A larger dose of glucagon administered by constant infusion virtually eliminated body weight gain over 7 days while significantly increasing nucleotide binding (GDP) to brown fat mitochondria. An important role for glucagon in thermogenic regulation is suggested.

Topics: Adipose Tissue, Brown; Animals; Blood Glucose; Body Temperature Regulation; Body Weight; Glucagon; Guanosine Diphosphate; Injections, Intraperitoneal; Insulin; Male; Mitochondria; Osmolar Concentration; Rats; Rats, Inbred Strains

The effects of essential fatty acid (EFA) deficiency on energetic metabolism and interscapular brown adipose tissue (BAT) activity were examined in the cold acclimated rat. Weanling male Long-Evans rats were fed on a low fat semipurified diet (control diet, 2% sunflower oil; EFA deficient diet, 2% hydrogenated coconut oil) for 9 weeks. They were exposed at 5 degrees C for the last 5 weeks. In EFA deficient rats, compared to controls, growth retardation reached 22% at sacrifice. Caloric intake being the same in the two groups, it follows that food efficiency was decreased by 40%. Resting metabolism in relation to body surface area was 25% increased. Calorigenic effect of norepinephrine (NE) in vivo (test of non-shivering thermogenesis) underwent a marked decrease of 34%. BAT weight was 21% decreased but total and mitochondrial protein content showed no variation. A 26% increase in purine nucleotide binding per BAT (taken as an index of thermogenic activity) was observed, suggesting that the enhancement in resting metabolism observed was mainly due to increased BAT thermogenesis. However, BAT mitochondria respiratory studies which are more direct functional tests showed a marked impairment of maximal O2 consumption of about 30% with palmitoyl-carnitine or acetyl-carnitine (both in presence of malate) or with alpha-glycerophosphate as substrate. It is likely that this impaired maximal BAT oxidative capacity may explain the impaired NE calorigenic effect in vivo. A possible increase in mitochondrial basal permeability is also discussed.

Topics: Acclimatization; Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Energy Metabolism; Fatty Acids, Essential; Guanosine Diphosphate; Male; Norepinephrine; Oxygen Consumption; Rats

A chronological study was performed to investigate the postnatal development of the thermogenic capacity of the brown adipose tissue (BAT) comparing rats born and reared at 16 degrees C (cold) or 28 degrees C (control). Mitochondrial mass, cytochrome-c-oxidase activity (index of oxidative capacity) and GDP binding to mitochondria (uncoupling test) were investigated in rats from 1 to 33 days of age. Specific cytochrome-c-oxidase activity was the same in both groups during the first week, then increased in the cold group and decreased in controls; from the 9th day it was always twice as high in the former as in the latter. Specific binding of GDP to mitochondrial proteins remained almost constant in control rats during the first week contrasting with a rapid increase in that for cold rats. Afterwards it decreased in both groups until weaning but remained five times as high in cold rats as in control rats. As growth of BAT is faster and mitochondrial content greater in cold reared rats, the capacity of the tissue for thermogenesis appeared to be greatly temperature dependent soon after birth and during the entire suckling period. However the mechanisms of this stimulation remain to be elucidated.

Topics: Adipose Tissue, Brown; Animals; Animals, Newborn; Binding Sites; Body Weight; Electron Transport Complex IV; Female; Guanosine Diphosphate; Mitochondria; Organ Size; Pregnancy; Proteins; Rats; Rats, Inbred Strains; Temperature

Oxygen consumption (VO2) and mitochondrial guanosine diphosphate (GDP) binding of interscapular brown adipose tissue (BAT) were measured in hypothyroid, hyperthyroid and euthyroid rats after stimulations with selective and nonselective beta-adrenoceptor agonists: BRL 35135A (BRL) and Isoprenaline (ISO). Resting VO2, VO2 increment and mitochondrial GDP binding after beta-adrenergic stimulations were lower in hypothyroid rats than in the euthyroid group. The reduced responses were more marked for ISO than for BRL. Restion VO2 and VO2 increment after beta-adrenergic stimulations were higher in hyperthyroid rats than in the eurthyroid group; the increment was more marked for BRL than for ISO. In hyperthyroidism, mitochondrial GDP binding after BRL and after ISO was in the same magnitude; it was higher in the hyperthyroid than in the euthyroid group after BRL but not after ISO. The different thermogenic responses after ISO and BRL stimulations suggest that BRL is acting on a beta-adrenoceptor differing from the beta-1 and beta-2 adrenoceptors responsible for the effects of ISO. Activation of thermogenesis via the beta-3 adrenoceptor seems to be less dependent on the permissive levels of thyroid hormones than activation via beta-1 and/or beta-2 adrenoceptors. The beta-3 adrenoceptor may be more sensitive to increased levels of thyroid hormones.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Guanosine Diphosphate; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Mitochondria; Organ Size; Oxygen Consumption; Rats; Rats, Inbred Strains; Reference Values; Thyroid Gland

Adrenalectomy arrests the development of obesity in ob/ob mice fed a high-starch diet and housed at a normal room temperature (20-25 degrees C) partly by stimulating the low thermogenic activity of brown adipose tissue (BAT). The present study was undertaken to determine if adrenalectomy would also lower energy retention and stimulate BAT metabolism in ob/ob mice housed in a warm environment (35 degrees C) where BAT thermoregulatory heat production is not needed. Adrenalectomy prevented hyperphagia and hyperinsulinemia and lowered the efficiency of energy retention in ob/ob mice housed at 35 degrees C, which is comparable to results obtained at 20-25 degrees C. Sympathetic nervous system stimulation of BAT (interscapular and subscapular depots) assessed by norepinephrine turnover was increased in adrenalectomized ob/ob mice. Thermogenic activity of BAT in adrenalectomized ob/ob mice (as assessed by GDP binding to isolated BAT mitochondria, GDP-inhibitable acetate-induced BAT mitochondrial swelling, and Mg2(/)-activated GDP binding to BAT mitochondria) was not elevated when results were expressed per milligram of mitochondrial protein but was elevated approximately 65% when expressed per interscapular and subscapular depots because adrenalectomy increased BAT mitochondrial mass. Adrenalectomy lowers the efficiency of energy retention and stimulates BAT metabolism even when ob/ob mice are housed in a warm environment.

Topics: Acetates; Adipose Tissue, Brown; Adrenalectomy; Animals; Body Temperature Regulation; Body Weight; Electron Transport Complex IV; Energy Metabolism; Female; Guanosine Diphosphate; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria; Mitochondrial Swelling; Myocardium; Norepinephrine; Reference Values

Central administration of 2-deoxy-D-glucose (2-DG) decreases brown fat thermogenesis. This effect is suggested to be mediated via a central control mechanism. Our study was designed to determine the importance of the sympathetic nervous system in the response of brown fat to intraperitoneal (i.p.) injection of 2-DG. Unilateral denervation of interscapular brown adipose tissue (IBAT) was performed on male Sprague-Dawley rats (300 g body weight). Nine days after surgery, rats were injected i.p. with either saline vehicle (0.9% sodium chloride) or 2-DG (360 mg/kg wt) and then killed one hour later. Sympathetic denervation resulted in 50% decreases in total IBAT protein and in mitochondrial protein recovered. In the denervated lobes, mitochondrial GDP binding (expressed as nmol/mg mitochondrial protein and as total activity recovered) was decreased to 36% and 18%, respectively. Injection of 2-DG did not change mitochondrial protein content in either the innervated or denervated IBAT. In the innervated lobes, 2-DG significantly lowered GDP binding to 55% of that in saline-treated animals, whether expressed per mg mitochondrial protein or as total recovered activity. In contrast, 2-DG did not further decrease GDP binding in the denervated lobes. In conclusion, the effects of i.p. injection of 2-DG on brown fat thermogenesis (as evidenced by GDP binding) appear to be primarily mediated via the sympathetic nervous system.

Topics: Adipose Tissue, Brown; Animals; Blood Glucose; Body Weight; Corticosterone; Deoxy Sugars; Deoxyglucose; Guanine Nucleotides; Guanosine Diphosphate; Insulin; Male; Mitochondria; Proteins; Rats; Rats, Inbred Strains; Sympathectomy; Sympathetic Nervous System

Hypothalamic and genetic obesities in rodents are usually associated with reproductive impairments, but the underlying etiology of the latter is not clear because of concomitant metabolic abnormalities in these animal models. In the present study metabolically intact rats were used and obesity was developed by offering the rats a cafeteria-type diet. Purina chow-fed animals were used as control. Cafeteria feeding was associated with hyperphagia and an increased brown adipose tissue (BAT) thermogenesis, in association with long estrous cycles (p less than 0.01). The latter was accounted for by a long diestrous phase (p less than 0.02). Replacement of the cafeteria diet with purina rat chow corrected the estrous cycle irregularities, as caloric consumption and body weight were reduced. We propose, as a working hypothesis, that reproductive functions are finely tuned with body temperature, and that an excess feeding-induced BAT thermogenesis may underlie the disruption in estrous cycle observed during overfeeding.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Eating; Energy Intake; Estrus; Female; Guanosine Diphosphate; Mitochondria; Rats; Rats, Inbred Strains

To clarify whether nicotine stimulates the sympathetic nervous system (SNS) and thermogenesis in brown adipose tissue (BAT) and whether it promotes the resting metabolic rate (RMR), with resulting mitigation of obesity, we measured norepinephrine (NE) turnover (an indicator of SNS activity), guanosine-5'-diphosphate (GDP) binding (a thermogenic indicator), oxygen consumption in BAT, and RMR in monosodium-L-glutamate (MSG) obese and saline control mice after 2 weeks treatment with nicotine. Nicotine significantly increased NE turnover, GDP binding, oxygen consumption in BAT, and RMR, and significantly reduced body weight in MSG obese mice as well as in control mice without affecting food intake. These results suggest that nicotine stimulates NE turnover and thermogenesis in BAT, and promotes RMR, all of which contribute to the mitigation of obesity.

Topics: Adipose Tissue, Brown; Animals; Basal Metabolism; Body Temperature Regulation; Body Weight; Eating; Female; Guanosine Diphosphate; Mice; Mice, Inbred ICR; Mitochondria; Nicotine; Norepinephrine; Obesity; Organ Size; Oxygen Consumption; Proteins; Sodium Glutamate

In euthyroid mice, a 48-h fast caused brown fat (BAT) atrophy characterized by loss of tissue proteins, succinate dehydrogenase (SDH), and a significant reduction in mitochondrial uncoupling protein (UCP) content. Chemical sympathectomy and surgical denervation failed to mimic the changes in BAT protein and SDH contents observed after food deprivation. However, suppression of sympathetic activity could account for the loss of UCP from the mitochondria. In mice made hyperthyroid by repeated triiodothyronine injections, losses of tissue SDH and proteins caused by food deprivation or surgical denervation were markedly suppressed, while the loss of UCP from the mitochondria remained unchanged. These results suggest that reduced sympathetic activity to BAT in fasted mice is not the exclusive cause of the tissue atrophy and that thyroid hormones may play a role in the control of brown fat atrophy in mice.

Topics: Adipose Tissue, Brown; Animals; Atrophy; Body Weight; Denervation; Energy Metabolism; Food Deprivation; Guanosine Diphosphate; Male; Mice; Mice, Inbred Strains; Mitochondria; Neurons; Succinate Dehydrogenase; Sympathectomy, Chemical; Thyroid Gland; Thyroid Hormones

1. The effects of riboflavin deficiency on growth, whole-body oxygen consumption, cytochrome c oxidase (EC 1.9.3.1) activity and GDP-binding capacity of brown adipose tissue were measured in three groups of rats: sucking pups, weanling rats, and dams. Control groups were weight-matched, pair-fed or fed ad lib. 2. Riboflavin deficiency reduced growth rate and increased the activation coefficient of erythrocyte glutathione reductase (NAD(P)H) (EC 1.6.4.2), as predicted. In sucking pups it also reduced whole-body O2 consumption per unit body-weight, especially after noradrenaline stimulation. In weanling rats, however, it increased O2 consumption both before and after noradrenaline stimulation. 3. Cytochrome c oxidase (EC 1.9.9.1) activity of brown adipose tissue was not consistently affected by riboflavin deficiency. Binding of [3H]GDP to the mitochondria was increased in the deficient weanling rats. 4. Weanling rats therefore, seemed better able to withstand the effects of severe depletion. Their reduced growth and increased non-shivering thermogenesis helped to counteract the unfavourable ratio of riboflavin:other tissue-building materials. The relevance for thermoregulation in riboflavin-deficient children is discussed.

Topics: Adipose Tissue, Brown; Animals; Animals, Newborn; Body Weight; Electron Transport Complex IV; Enzyme Activation; Glutathione Reductase; Guanosine Diphosphate; Mitochondria; Norepinephrine; Organ Size; Oxygen Consumption; Rats; Riboflavin Deficiency; Weaning

The effect of exercise training on brown adipose tissue (BAT) thermogenesis was studied by measuring cytochrome oxidase activity, as a marker of mitochondrial abundance, mitochondrial guanosine-5'-diphosphate (GDP) binding, as an indicator of thermogenic activity and oxygen consumption in BAT in ovariectomized (OVX) obese rats and sham-operated rats. Six-week exercise training significantly suppressed body weight gain in OVX rats to the level of sedentary control rats, although food intake in exercise trained OVX rats increased more than in the sedentary OVX rats. Exercise training increased cytochrome oxidase activity, mitochondrial GDP binding and oxygen consumption in BAT in OVX rats, which were reduced in a sedentary condition, as well as in the control rats. These results suggest that exercise training potentiates BAT thermogenesis, which may contribute to the reduction of body weight in OVX obese rats.

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Eating; Electron Transport Complex IV; Female; Guanine Nucleotides; Guanosine Diphosphate; Ovariectomy; Oxygen Consumption; Physical Exertion; Rats; Rats, Inbred Strains

1. The consequences of essential fatty acid (EFA) deficiency on the resting metabolism, food efficiency and brown adipose tissue (BAT) thermogenic activity were examined in rats maintained at thermal neutrality (28 C). 2. Weanling male Long-Evans rats were fed a hypolipidic semi-purified diet (control diet: 2% sunflower oil; EFA-deficient diet: 2% hydrogenated coconut oil) for 9 weeks. 3. They were kept at 28 C for the last 5 weeks. Compared to controls, in EFA-deficient rats the growth shortfall reached 21% at killing. 4. As food intake was the same in EFA-deficient and control rats, food efficiency was thus decreased by 40%. 5. Resting metabolism expressed per surface unit was 15% increased. 6. Non-renal water loss was increased by 88%. 7. BAT weight was 28% decreased but total and mitochondrial proteins were not modified. 8. Heat production capacity, tested by GDP binding per BAT was 69% increased in BAT of deficient rats. 9. The stimulation of BAT was established by two other tests: GDP inhibition of mitochondrial O2 consumption and swelling of mitochondria. 10. It is suggested that the observed enhancement of resting metabolism in EFA-deficient rats is, in part, due to an activation of heat production in BAT.

Topics: Adipose Tissue, Brown; Animals; Body Temperature; Body Weight; Electron Transport Complex IV; Energy Metabolism; Fatty Acids, Essential; Guanosine Diphosphate; Male; Mitochondria; Mitochondrial Swelling; Oxygen Consumption; Rats

Adrenalectomy (ADX) prevents the excessive weight gain in the genetically obese ob/ob and db/db mice. To test the possibility that this results from increased energy expenditure due to increased thermogenesis in brown adipose tissue (BAT), we measured GDP binding to mitochondria from interscapular brown adipose tissue (BAT) in db/db and ob/ob mice and their lean controls after adrenalectomy, with and without corticosterone replacement. Both the vehicle treated and corticosterone treated db/db and ob/ob mice had lower body weights than the sham-operated mice GDP binding to mitochondria from IBAT was significantly lower in both the db/db and ob/ob mice than in their lean controls. Adrenalectomy significantly increased GDP binding in all mice compared to the respective sham-operated mice, but, the percentage increase was always greater in the db/db and ob/ob mice. Corticosterone treatment of adrenalectomized db/db, ob/ob or lean mice lowered GDP binding to sham levels. Our data confirm previous findings that adrenalectomy results in increased GDP binding to mitochondria from IBAT. Injections of corticosterone into adrenalectomized mice results in a decrease in GDP binding to values which are similar to values in sham-operated mice. Thus adrenalectomy may inhibit the development of obesity by increasing the thermic activity in IBAT.

Topics: Adipose Tissue; Adrenalectomy; Animals; Body Temperature Regulation; Body Weight; Corticosterone; Diabetes Mellitus, Experimental; Guanosine Diphosphate; Male; Mice; Mice, Mutant Strains; Mice, Obese

Our previous work showed that ob/ob mice responded to physiological concentrations of blood corticosterone (maintained by implanted pellets of corticosterone in adrenalectomized mice) by increasing food intake and blood insulin concentration to a much greater extent than did lean mice. The present study sought to determine whether the chronic presence of corticosterone was necessary or whether a single injection would also have these effects. Lean and ob/ob mice were adrenalectomized at 4.5 wk of age, injected with corticosterone at 10.5 wk of age, and killed 6 or 15 h after injection. A markedly exaggerated hyperinsulinemia was seen in ob/ob mice at 15 h. Food intake increased in both lean and obese mice, and brown adipose tissue thermogenesis (as reflected by mitochondrial guanosine 5'-diphosphate binding) was suppressed in both. We conclude that the ob/ob mouse has an excessive central sensitivity and responsiveness to a rapid action of corticosterone that results in neural activation of insulin secretion and suppression of brown adipose tissue thermogenesis. The persistence of some degree of obesity in the adrenalectomized ob/ob mouse is attributed to the remaining slight hyperinsulinemia coupled with reduced energy expenditure due to persistent thermoregulation at a lower than normal body temperature.

Topics: Adipose Tissue, Brown; Adrenalectomy; Animals; Blood Glucose; Body Composition; Body Temperature; Body Weight; Corticosterone; Drug Implants; Feeding Behavior; Female; Guanosine Diphosphate; Insulin; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria; Reference Values

Three experiments have examined the interaction of adrenalectomy and fenfluramine on food intake, body weight and the binding of guanosine-5'-diphosphate (GDP) to interscapular brown adipose tissue (IBAT). In the first experiment, GDP-binding by IBAT mitochondria from adrenalectomized or sham-operated animals was measured for 3 hr after one of 3 doses of fenfluramine. Fenfluramine stimulated GDP-binding at lower doses in the adrenalectomized animals than in the controls. In the first chronic experiment, adrenalectomy prevented the restoration of normal food intake observed 8-10 days after the beginning of fenfluramine treatment. Adrenalectomy also increased weight loss and enhanced GDP binding to mitochondria from IBAT in rats treated with fenfluramine. In the second chronic experiment, the combination of fenfluramine and adrenalectomy led to a progressive weight loss, continuing hypophagia and stimulation of GDP-binding by IBAT, whereas rats treated with fenfluramine alone showed a recovery of food intake at a stabilized but lower body weight. These data are consistent with the hypothesis that adrenalectomy and fenfluramine disable two separate components of the food intake system and that when combined, produce a profound and persisting disturbance in energy or nutrient balance.

Topics: Adipose Tissue, Brown; Adrenalectomy; Animals; Body Weight; Cholesterol; Corticosterone; Dose-Response Relationship, Drug; Drug Implants; Eating; Female; Fenfluramine; Guanosine Diphosphate; Mitochondria; Rats; Rats, Inbred Strains

The effect of hibernation and arousal on brown adipose tissue (BAT) cytochrome-c oxidase activity and GDP binding, as well-circulating metabolites, have been studied in the 13-lined ground squirrel. Control animals (warm adapted) were housed continuously at 23 degrees C, while the remaining animals were transferred into a cold room (4 degrees C) for 8 days to induce hibernation. Hibernating animals were killed while deeply hibernating. Aroused animals were manually stimulated to induce arousal or had spontaneously aroused on the day of the experiment. BAT weight as well as mitochondrial mass were increased in both groups of cold-adapted animals, relative to controls. A substantial increase in GDP binding, however, was seen only in aroused animals, an observation confirmed by Scatchard analysis. Arousal was also accompanied by marked alterations in the levels of several circulating metabolites. Plasma free fatty acids declined by approximately 20% despite a three- to fourfold increase in plasma glycerol concentrations. Plasma lactate levels increased eightfold, while concentrations of beta-hydroxybutyrate were five times lower during arousal than hibernation. These data are consistent with the idea that the oxidation of free fatty acids, glucose, and ketone bodies are all increased during arousal. In conclusion, we have found that cold adaptation and subsequent hibernation increases BAT thermogenic capacity in the 13-lined ground squirrel. However, this increase in thermogenic potential is not manifested as a substantial increase in BAT thermogenic activity until arousal is initiated.

Topics: Adipose Tissue, Brown; Animals; Arousal; Body Weight; Guanine Nucleotides; Guanosine Diphosphate; Hibernation; Mitochondria; Organ Size; Sciuridae

Corticotropin-releasing factor (CRF) has been administered into the third ventricle of sham-operated and ventromedial hypothalamic (VMH)-lesioned rats in acute and chronic experiments. After a single 5-microgram injection of CRF, there was an acute reduction of food intake in both sham-operated and VMH-lesioned rats that persisted for 3 h. The effect was still present in the VMH-lesioned rats between 3 and 6 h but had dissipated in the sham-operated controls. Guanosine 5'-diphosphate (GDP) binding to mitochondria from interscapular brown adipose tissue was used as an index of thermogenic activity in this tissue. In 21-h food-deprived rats, GDP binding was significantly lower in VMH-lesioned than in sham-operated animals. Although the mean increase in sham-operated animals was increased, this was not significantly different from saline-injected controls. In the VMH-lesioned rats, however, CRF acutely increased GDP binding to values not different than those of the sham-operated controls. Serum corticosterone was significantly lower in the VMH-lesioned rats, but both groups showed a significant stimulation by CRF during a 7-day infusion of CRF (4.8 micrograms/day) into the third ventricle. Food intake was significantly depressed in the VMH-lesioned animals that received CRF, from values of 35 g/day to approximately 25 g/day. Body weight showed a slow steady decrease, having fallen by nearly 15 g at the end of the 7-day infusion period. In contrast the mean value in the VMH-lesioned controls had significantly higher in CRF-infused animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue, Brown; Animals; Blood Glucose; Body Weight; Cerebral Ventricles; Corticosterone; Corticotropin-Releasing Hormone; Feeding Behavior; Female; Guanosine Diphosphate; Infusions, Parenteral; Mitochondria; Organ Size; Rats; Rats, Inbred Strains; Reference Values; Ventromedial Hypothalamic Nucleus

Corticotropin releasing factor (CRF) has been administered into the third ventricle of lean and genetically obese Zucker fatty rats in both acute and chronic experiments. Following a single injection of CRF (5 micrograms or approximately 1 nmole) there was an acute reduction of food intake in both the lean and obese animals, but the effect was greater in the obese. This effect persisted for the first three hours but was no longer detectable in either lean or genetically obese animals at 6 hours. Binding of GDP to mitochondria from interscapular brown adipose tissue in 21-hour deprived animals was lower in the fatty rats than in the lean controls. The injection of CRF significantly increased GDP binding in both the lean and fatty rats. During chronic infusion of CRF into the third ventricle of fatty rats, there was a significant decrease in food intake in the obese rats and fall of body weight in both groups. The basal levels of GDP binding were significantly lower in the saline-infused fatty rats than in the saline-infused lean controls. The chronic infusion of CRF increased GDP binding in the fatty rats but not in the lean animals. The CRF-treated values for GDP binding in fatty rats however, remained significantly below the baseline values in the control animals. Chronic CRF infusion also significantly lowered glucose levels in the fatty rat. These studies are consistent with the hypothesis that CRF may be involved in the decreased food intake and increased sympathetic activity observed in genetically obese fatty rats following adrenalectomy.

Topics: Adipose Tissue, Brown; Animals; Behavior, Animal; Blood Glucose; Body Weight; Corticosterone; Corticotropin-Releasing Hormone; Feeding Behavior; Guanosine Diphosphate; Male; Mitochondria; Organ Size; Rats; Rats, Zucker; Time Factors

Animals with the viable yellow (Avy/a) gene and their corresponding lean control black mice (a/a) were adrenalectomized or sham adrenalectomized, and changes in body weight, body composition, corticosterone, and GDP-binding to mitochondria isolated from interscapular brown adipose tissue (IBAT) were measured. Adrenalectomy slowed the weight gain of both the yellow obese mice and the black lean mice, but the reduction was greater in the yellow mice. Food intake was significantly reduced in the yellow mice. Adrenalectomy in the yellow mouse was associated with an increase in lean mass and a significant decrease in weights of fat depots. Blood glucose concentrations of the adrenalectomized yellow mice were reduced to levels similar to those of lean mice, but insulin levels, although lower than sham-adrenalectomized yellow mice, remained significantly higher than in lean animals. GDP binding to IBAT mitochondria increased after adrenalectomy in both phenotypes to values that were similar. Corticosterone replacement in adrenalectomized yellow mice produced a dose-dependent increase in body weight that was associated with a decrease in muscle weight and an increase in adipose tissue weight. Both desacetyl-melanocyte-stimulating hormone (MSH) and alpha-MSH interacted with corticosterone to increase body weight gain of adrenalectomized yellow mice. Desacetyl-MSH was more effective than alpha-MSH on increasing adipose tissue and liver weights. The effects of desacetyl-MSH on food intake, weight gain, and tissue weights were independent of the adrenal gland or of corticosterone.

Topics: Adipose Tissue, Brown; Adrenalectomy; Animals; Body Weight; Corticosterone; Feeding Behavior; Guanosine Diphosphate; Male; Melanocyte-Stimulating Hormones; Mice; Mice, Obese; Mitochondria; Organ Size; Reference Values

The effects of fasting and refeeding on nonshivering thermogenesis and the properties of brown adipose tissue have been investigated in mice. Fasting for 48 h led to a substantial reduction in the capacity for nonshivering thermogenesis, and there was no recovery of thermogenic capacity during the first 5 days of refeeding. A period of 10-15 days of refeeding was required for full restoration of thermogenic capacity. The mice were hyperphagic during the first 6 days of refeeding, but body weight was recovered after 24 h. The amount of interscapular brown adipose tissue decreased substantially on fasting, but it recovered 24 h after the initiation of refeeding. Cytochrome oxidase activity, the level of mitochondrial GDP binding, and the specific mitochondrial concentration of uncoupling protein in brown adipose tissue were each reduced by fasting. Although both GDP binding and the specific concentration of uncoupling protein rapidly returned to normal on refeeding, the activity of cytochrome oxidase was not normalized until 10 days after the end of the fast. These results indicate that a prolonged period of refeeding is required for the recovery in the capacity for nonshivering thermogenesis following a fast, a similar time course being evident for the recovery of cytochrome oxidase activity in brown adipose tissue. It is suggested that the fasting-induced reduction in the capacity for nonshivering thermogenesis is linked primarily to a loss of mitochondria from brown adipose tissue and that the normalization of thermogenic capacity is dependent on the restoration of mitochondrial mass.

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Electron Transport Complex IV; Energy Intake; Fasting; Food; Guanosine Diphosphate; Male; Mice; Mice, Inbred C57BL

Hypocaloric diet (control diet diluted 1:1 with cellulose) feeding during pregnancy caused a reduction in the body weight of rat pups at birth whereas the main parameters of brown adipose tissue composition and thermogenic activity were unaffected. When prenatally underfed rat pups were nursed by untreated dams eating control diet during lactation, early (day 4 of life) and late (day 13 of life) neonatal body weight was rehabilitated and brown adipose tissue remained essentially unchanged. When prenatally underfed rat pups were nursed by dams that were fed with the hypocaloric diet during lactation, neonatal body weight continued lower at the two mentioned days of life and the overall thermogenic capacity of brown fat (GDP binding/g body weight) was substantially depressed. The reduction of the brown fat thermogenic capacity in these pups is mainly due to a hypotrophy of the mitochondrial component of the tissue as indicated by the lowered cytochrome oxidase activity. Results indicate that mild maternal underfeeding during lactation may depress brown adipose tissue thermogenic function in neonates whereas similar hypocaloric intakes during pregnancy did not alter brown fat thermogenic capacity.

Topics: Adipose Tissue, Brown; Animals; Animals, Newborn; Birth Weight; Body Temperature Regulation; Body Weight; Electron Transport Complex IV; Energy Intake; Female; Guanosine Diphosphate; Lactation; Litter Size; Mitochondria; Organ Size; Pregnancy; Rats; Rats, Inbred Strains

This study has tested the hypothesis that nicotine might increase thermogenesis in rats by activating the sympathetic nervous system which supplies brown adipose tissue. Three hours after a single injection of nicotine, both the turnover of norepinephrine and the binding of the purine nucleotide, guanosine 5'-diphosphate (GDP) to mitochondria from brown adipose tissue were significantly increased. After 11 days of treatment with nicotine, the turnover of norepinephrine and the GDP binding to mitochondria from brown adipose tissue both remained elevated but weight gain was not different. These data are consistent with the hypothesis that nicotine may have part of its effect through changes in thermogenesis involving sympathetic nervous activation of peripheral thermogenic tissues such as brown adipose tissue.

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Eating; Guanosine Diphosphate; Indicators and Reagents; Mitochondria; Nicotine; Norepinephrine; Rats

Thermogenesis of brown adipose tissue (BAT) of genetically obese mice, KKAY mice, was examined by measuring the BAT mitochondrial guanosine diphosphate (GDP) binding as an index of thermogenesis and comparing it with that of normal C57BL mice. No great difference in GDP binding was observed in KKAY and C57BL mice fed a stock diet. However, when they were given a sucrose solution, the increase in BAT mitochondrial GDP binding of KKAY mice (+22%) was much lower than that of C57BL mice (+106%). A high fat diet increased BAT mitochondrial GDP binding in KKAY mice to the same extent (+82%) as in C57BL mice. When the mice were fasted for 48 h, BAT mitochondrial GDP binding of C57BL mice decreased by 70%, while that of KKAY mice showed no change. Both acute exposure to cold and norepinephrine injections increased GDP binding in KKAY mice by 90% and 131%, respectively. These results indicate that low BAT thermogenesis in response to sucrose intake may be a cause of obesity in KKAY mice, and this may be brought about by defects in the central nervous system.

Topics: Adipose Tissue, Brown; Aging; Animals; Body Temperature Regulation; Body Weight; Diabetes Mellitus; Fasting; Female; Guanosine Diphosphate; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria; Sucrose

Despite long-standing observations of a whole-body thermogenic effect of glucagon, the role of glucagon in activating thermogenesis in brown adipose tissue has not often been studied. We investigated the ability of administered glucagon to produce alterations in brown adipose tissue similar to changes produced by accepted stimuli of brown fat activity: cold, norepinephrine, and overfeeding. Eighteen days of glucagon injections (1 mg/kg) to male Sprague-Dawley rats produced, relative to saline-injected controls, decreases in feed efficiency and increases in brown adipose tissue weight, protein content, DNA content, and mitochondrial mass as reflected in cytochrome oxidase activity. The observed changes were similar, though of lesser magnitude, to changes produced in these same parameters induced by administration of norepinephrine (250 micrograms/kg) for a positive control group. Four days of glucagon administration (1 mg/kg) produced increases in specific activity of cytochrome oxidase and lipoprotein lipase. After 8 days of glucagon administration, changes in whole-pad activity similar to those seen with 18 days of administration were present. Glucagon also increased whole-pad lipoprotein lipase activity after 4 and 8 days. Surgically denervated interscapular brown adipose tissue retained its ability to respond to exogenous glucagon, though the magnitude of the response was diminished. Guanosine 5'-diphosphate (GDP) binding to brown adipose tissue mitochondria was measured as an assessment of functional state after 5 days of glucagon (1 mg/kg). There was an increase in GDP binding relative to controls whether expressed as picomoles per milligram mitochondrial protein or nanomoles per pad.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; DNA; Electron Transport Complex IV; Glucagon; Guanosine Diphosphate; Lipoprotein Lipase; Male; Norepinephrine; Rats; Rats, Inbred Strains

Mice selectively bred for either high or low levels of thermoregulatory nest building were cold-acclimated (5 degrees C) for 3 weeks without nesting material; then body weight and food intake were measured. The mice selected for low nest building (Lows) of both sexes showed lower feed efficiencies than the high nest-building mice (Highs), although their body weights were not significantly different (Table 1). This adds to a large body of evidence which suggests that nest building and feed efficiency were influenced by a common mechanism (Lacy et al. 1978; Sulzbach and Lynch 1984; Lynch et al. 1981; Lynch and Roberts 1984). Brown adipose tissue mitochondrial GDP binding and cytochrome c oxidase activity were measured in the above mice. In females, the Lows had 100% higher levels of total GDP binding than the Highs, while no difference between the lines was seen in males. Thus in the High females, lower energy expenditure through brown fat thermogenesis may account for their greater feed efficiency. In males, the genetic differences in feed efficiency must be due to differences in either thermogenesis in tissues other than brown fat, or mechanisms which reduce heat loss.

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Cold Temperature; Electron Transport Complex IV; Energy Intake; Female; Guanosine Diphosphate; Male; Mice; Mitochondria; Nesting Behavior; Selection, Genetic; Sex Characteristics

The effect of electrolytic lesions in the ventromedial hypothalamus (VMH) and the paraventricular nucleus (PVN) has been compared during both the dynamic and static phase of weight gain. Hyperphagia and weight gain were greater in the VMH-lesioned rats than in the PVN-lesioned rats. Food intake increased at night after both lesions but increased in the daytime only in VMH-lesioned rats. During the dynamic phase of rapid weight gain, the diurnal pattern of corticosterone was blunted to a similar degree in both lesioned groups. The morning insulin concentrations were higher in both lesioned groups than in the sham-operated controls, but in the static phase only the VMH-lesioned rats had higher insulin levels. In the afternoon the insulin was higher in the VMH-lesioned rats than in either the sham-operated or PVN-lesioned rats. In the dynamic phase the weight of interscapular brown adipose tissue was significantly increased in the VMH-lesioned rats, but the specific GDP binding was depressed both in the morning and afternoon when compared with either the sham-operated or PVN-lesioned groups. In both the dynamic and static phases GDP binding was similar in sham-operated and PVN-lesioned animals. The differences in concentration of corticosterone in morning and afternoon were smaller in the lesioned groups than in the controls. These data are consistent with the hypothesis that animals with PVN lesions do not show the disturbances in food intake or in the autonomic nervous system that characterize the VMH-lesioned rats.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Circadian Rhythm; Corticosterone; Energy Intake; Female; Guanosine Diphosphate; Insulin; Mitochondria; Obesity; Paraventricular Hypothalamic Nucleus; Rats; Time Factors; Ventromedial Hypothalamic Nucleus

The attenuated thermogenic responses observed in older animals exposed to low environmental temperatures may reflect decreased thermogenic capacity of brown adipose tissue, a major nonshivering thermogenic effector in rats, and/or decreased metabolic capacity of lean body mass. To evaluate these possibilities, the oxygen consumption of female Sprague-Dawley rats aged 5 and 26 months was recorded at rest and during 6 h of exposure to 6 degrees C. The thermogenic capacity of brown fat was estimated from the binding of guanosine-5'-diphosphate (GDP) to isolated brown fat mitochondria. Both resting and cold-induced oxygen consumption expressed on a mass independent basis [ml/(min x kg body mass.67)] and as a function of lean body mass [ml/(min x g lean body mass)] were significantly lower in the 26-month-old animals. Colonic temperatures of younger and older rats after the 6 h of cold exposure were 37.5 +/- 0.1 and 36.1 +/- 0.2 degrees C, respectively, and were significantly different. However, no significant differences in the binding of GDP to isolated brown fat mitochondria were observed. These data indicate that the thermogenic capacity of brown fat is not decreased in the aged rat, and that the metabolic capacity as well as the amount of lean body mass is altered with age.

Topics: Adipose Tissue, Brown; Aging; Animals; Body Temperature Regulation; Body Weight; Cold Temperature; Female; Guanine Nucleotides; Guanosine Diphosphate; Mitochondria; Oxygen Consumption; Rats; Rats, Inbred Strains

The influence of diet on the response of lean and obese fa/fa rats to adrenalectomy has been studied. Adrenalectomized and sham-operated rats were fed either a semi-synthetic high-carbohydrate (HC) or high-fat (HF) diet for 13 days. Energetic efficiency, calculated for measurements of energy storage and energy intake, was increased in obese rats fed both HC and HF diets and reduced close to values of lean rats after adrenalectomy. Brown adipose tissue mitochondrial GDP binding and uncoupling protein concentration were reduced in control obese rats fed both HC and HF diets. After adrenalectomy the level of GDP binding and uncoupling protein concentration were increased to levels of lean rats. Molar ratios of GDP binding to uncoupling protein were similar in lean and obese rats, were unaffected by adrenalectomy, but were elevated in rats fed the HC diet (0.40 +/- 0.02 vs 0.28 +/- 0.03). The data suggests that diet, but not obese genotype, may influence the masking of mitochondrial uncoupling protein.

Topics: Adipose Tissue, Brown; Adrenalectomy; Animals; Body Composition; Body Weight; Carrier Proteins; Dietary Carbohydrates; Dietary Fats; Energy Intake; Energy Metabolism; Guanosine Diphosphate; Ion Channels; Male; Membrane Proteins; Mitochondria; Mitochondrial Proteins; Obesity; Rats; Rats, Zucker; Uncoupling Agents; Uncoupling Protein 1

Daily injection of lean Zucker rats with a beta 2-adrenergic agonist (clenbuterol, 1 mg/kg) for 22 day increased weight gained by 38 per cent; there were significant increases in carcass protein and water, but fat content was unaltered. Clenbuterol did not affect energy intake or expenditure, the acute thermogenic response to food, or brown adipose tissue (BAT) activity (assessed from mitochondrial purine nucleotide (GDP) binding). In obese Zucker rats, clenbuterol significantly depressed energetic efficiency and increased the thermogenic response to food and BAT activity in these mutants. Body weight gain was not significantly affected by clenbuterol in obese Zucker rats but this was because of a 19 per cent reduction in fat content accompanied by a simultaneous 13 per cent increase in protein content. The ratio of protein/fat gained during the study was increased by 50 and 173 per cent by clenbuterol in lean and obese rats, respectively. Thus, clenbuterol exhibits potent anabolic effects on lean body mass in genetically obese as well as lean rats, but also increases thermogenesis and reduces body fat content in the obese mutants.

Topics: Adipose Tissue, Brown; Animals; Body Composition; Body Temperature Regulation; Body Weight; Clenbuterol; Eating; Energy Intake; Energy Metabolism; Ethanolamines; Food; Guanosine Diphosphate; Male; Mitochondria; Obesity; Oxygen Consumption; Rats; Rats, Zucker

Adrenalectomy normalizes many abnormalities of the obese (ob/ob) mouse. The high corticosterone concentration in blood may account in part for development of obesity and other abnormalities in the ob/ob mouse. Our objective was to determine dose-response relationships for the effect of corticosterone on the obesity. Lean and ob/ob mice were adrenalectomized or sham-operated at 4.5 wk of age. Adrenalectomized mice received 100 mg implants of cholesterol containing corticosterone (0, 2, 5, 20, or 50 mg) at 8.5 wk of age and were killed at 10.5 wk of age. In ob/ob mice, but not in lean mice, low physiological levels of serum corticosterone (up to 10 micrograms/dl) markedly increased body weight gain, food intake, and serum insulin. They also increased white and brown adipose tissue weights and decreased brown adipose tissue mitochondrial GDP binding. Higher levels of corticosterone (12-22 micrograms/dl) increased body weight gain, white and brown adipose tissue weights, and serum insulin and suppressed brown adipose tissue mitochondrial GDP binding in lean mice also, although in most cases to a lesser extent than in ob/ob mice, but were still without effect on food intake. Only very high levels of corticosterone (approximately 30 micrograms/dl) increased food intake in lean mice. Hyperglycemia was induced in ob/ob, but not lean, mice only at concentrations of corticosterone greater than 17 micrograms/dl. Thermoregulation was unaffected by serum corticosterone at levels from 0 to 30 micrograms/dl in both ob/ob and lean mice. Thus the ob/ob mouse is excessively sensitive and responsive to an effect of physiological levels of corticosterone that results in hyperphagia, hyperinsulinemia, and increased weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue; Adipose Tissue, Brown; Adrenalectomy; Animals; Blood Glucose; Body Temperature; Body Weight; Corticosterone; Dose-Response Relationship, Drug; Eating; Female; Guanosine Diphosphate; Insulin; Mice; Mice, Inbred C57BL; Mitochondria; Obesity; Organ Size

Complete energy balance measurements were made in exercise-trained (treadmill running) rats subjected to 27 d of exercise detraining. The 20% difference in body-weight that existed at the end of the training period between sedentary and trained rats was negated by detraining. Detrained rats had twice the body-weight gain of their untrained controls. An elevation (12%) in metabolizable energy (ME) intake (relative to body-weight) was observed in detrained rats while their gross energetic efficiency was augmented by 60%. Energy expenditure, excluding the estimated costs of fat and protein storage, was similar for detrained and untrained rats. Complementing the latter was the finding that thermogenesis in brown adipose tissue, a known energy buffering process, was also similar. Elevated ME intake (relative to body-weight) largely contributed to the increased energetic efficiency of detrained rats.

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Eating; Energy Metabolism; Guanosine Diphosphate; Lipid Metabolism; Male; Physical Exertion; Proteins; Rats; Rats, Inbred Strains

Male Sprague-Dawley rats were treated with a usually lethal dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 125 micrograms/kg i.p. in corn oil) or with vehicle alone. Two, 4, and 8 days after treatment the temperature of interscapular brown adipose tissue (IBAT) was monitored during venous infusion of norepinephrine (480 ng/min) for 60 min. The temperature response was about 1.0-1.5 degrees C within 1 h in vehicle-treated, pair-fed and ad libitum-fed controls. In TCDD-treated animals, the response of IBAT decreased with time after TCDD dosage, amounting to only 0.3 +/- 0.1 degree C at 8 days after dosing (differences significant with respect to both controls, P less than 0.05). GDP binding to IBAT mitochondria (a measure of thermogenic capacity) was unchanged in all groups, indicating that the reduced thermogenic response was probably not caused by an impairment of the mitochondrial uncoupling process by TCDD.

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Dioxins; Eating; Guanosine Diphosphate; Male; Norepinephrine; Polychlorinated Dibenzodioxins; Rats; Rats, Inbred Strains

The effects of chronic feeding of a high-fat diet or a cafeteria-type diet on weight gain and thermogenesis in brown adipose tissue as measured by the binding of a purine nucleotide (guanosine 5'-diphosphate, GDP) to mitochondria of brown adipose tissue have been studied in two strains of rats that differ in their susceptibility to dietary obesity. S 5B/Pl rats, which are resistant to developing obesity when eating a high-fat diet or drinking sucrose solutions, have greater specific GDP binding in interscapular brown adipose tissue (IBAT) than do Osborne-Mendel rats, which are sensitive to fat-induced obesity. A high-fat diet, fed isoenergetically to the low-fat diet, did not increase the growth of IBAT and decreased specific GDP binding in both strains. Feeding a cafeteria diet resulted in obesity and increased mass and protein content of the IBAT in both strains of rats. However, specific GDP binding increased in response to cafeteria feeding only in the Osborne-Mendel rats. These studies show that thermogenesis, as measured by GDP binding to mitochondria in brown adipose tissue, is suppressed by both isoenergetic and ad libitum feeding of a high-fat diet. The higher basal GDP binding in the brown fat of the S 5B/Pl rats suggests that higher thermogenesis of this tissue contributes to the resistance of this strain to fat-induced obesity. The inability of S 5B/Pl rats to further increase thermogenesis when eating a cafeteria diet may contribute to their becoming obese.

Topics: Adipose Tissue, Brown; Animals; Body Composition; Body Temperature Regulation; Body Weight; Dietary Fats; Disease Models, Animal; Disease Susceptibility; Guanosine Diphosphate; Obesity; Organ Size; Rats

Mice treated with glutamate in the neonatal period are known to develop into stunted obese adults, despite hypophagia. Our objective was to find out whether brown adipose tissue (BAT) thermogenic function might be abnormal in the glutamate-obese mouse. At 10 wk of age, group-housed glutamate-obese mice exhibited nocturnal and early diurnal torpor, i.e., they thermoregulated at a lower than normal body temperature. When exposed to 4 degrees C, they died in hypothermia within 24 h. They could adapt to living at 14 degrees C for up to 1 wk but failed to adjust their food intake sufficiently to maintain their body weight. Their fat stores were, nevertheless, conserved. BAT was present in increased amounts in glutamate-obese mice. Its thermogenic activity (as assessed by the level of mitochondrial GDP binding) was normal (male mice) or reduced (female mice). A normal thermogenic responsiveness of BAT to cold occurred. The thermogenic response of BAT to a cafeteria diet was normal (male mice) or reduced (female mice). Serum corticosterone concentration was increased in both male and female glutamate-treated mice particularly in the cold. We conclude that the high metabolic efficiency and obesity of the glutamate-obese mouse are principally a consequence of its maintenance of a hypothermic torpid state for more than 50% of the time. An additional deficit in energy expenditure in female, but not male, glutamate-obese mice is associated with suppressed responsiveness of the thermogenic function of BAT to diet and may account for the greater degree of obesity in female than in male glutamate-treated mice.

Topics: Acclimatization; Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Circadian Rhythm; Cold Temperature; Eating; Female; Glutamates; Glutamic Acid; Guanosine Diphosphate; Male; Mice; Mice, Inbred C57BL; Obesity; Organ Size; Sex Factors

Effects of hyper- and hypothyroidism on catecholamine (CA) metabolism in the brain, adrenal glands, liver, and brown adipose tissue (BAT) were studied in adult rats during cold acclimation. Hypothyroidism was induced by the administration of propylthiouracil (PTU) and hyperthyroidism by the injection of thyroxine (T4). After 2 weeks of treatment, they were exposed to cold (5 degrees C) and sacrificed after 1 or 4 weeks. Although the body weight gain of PTU-treated rats were markedly impaired, the body temperature was maintained within normal range. They had increased cerebral dopamine, adrenal CA and BAT norepinephrine (NE) contents, enhanced cerebral tyrosine hydroxylase and adrenal dopamine beta-hydroxylase (DBH) activities and elevated [3H]dihydroalprenolol (DHA) binding to liver plasma membranes (P less than 0.01 vs controls). T4-treated rats showed an increased brain and adrenal CA only after cold exposure. The BAT NE content, DHA binding to liver plasma membranes, and [3H]guanosine diphosphate binding to BAT mitochondria were reduced by 30 to 50% from control values after 4 weeks of cold exposure. These results indicate that during cold acclimation, thyroid hormone deficiency is associated with an accelerated CA synthesis and release, which results in an enhanced BAT thermogenesis, and the hyperthyroid state suppresses CA release, hepatic DHA binding, and BAT heat production. Thus, there is a close metabolic interrelationship between thyroid hormone and CA during exposure to cold. CA appears to ameliorate thyroid hormone excess or deficiency.

Topics: Acclimatization; Adipose Tissue, Brown; Adrenal Glands; Animals; Body Temperature Regulation; Body Weight; Brain; Catecholamines; Cold Temperature; Dihydroalprenolol; Energy Metabolism; Guanosine Diphosphate; Liver; Rats; Rats, Inbred Strains; Thyroid Hormones; Tyrosine 3-Monooxygenase

Syrian hamsters (Mesocricetus auratus) were fed a high-fat (HF) diet for up to 16 wk. Sympathetic and thermogenic activities in their brown adipose tissue (BAT) were assessed by measuring norepinephrine content and turnover and mitochondrial GDP binding and cytochrome c oxidase activity. Chronic ingestion of the HF diet resulted in significant increases in carcass lipid and interscapular BAT wet weight by the end of the second week. HF-fed hamsters were slightly hyperphagic during the first 2 wk of HF feeding only. Significant weight gains persisted beyond the period of hyperphagia. Hypertrophy of interscapular BAT after 16 wk on the HF diet was accompanied by increases in protein and DNA content, indicating growth of functional tissue. Norepinephrine turnover and content in BAT were decreased throughout the entire period of HF feeding, regardless of changes in caloric intake or body weight. Mitochondrial cytochrome c oxidase activity and GDP binding were increased after 16 wk on the HF diet, a time when the HF-fed animals were obese but not hyperphagic. These results demonstrate a dissociation of BAT thermogenesis from sympathetic activity in the tissue. It appears that sympathetic nervous system activity in BAT was suppressed by the HF diet, whereas thermogenic activity of the tissue was activated when the hamsters became obese.

Topics: Adipose Tissue, Brown; Animals; Body Composition; Body Temperature Regulation; Body Weight; Cricetinae; Dietary Fats; DNA; Eating; Electron Transport Complex IV; Guanosine Diphosphate; Male; Mesocricetus; Mitochondria; Norepinephrine; Sympathetic Nervous System

This experiment examined the effect of short photoperiod on food intake, body weight, carcass composition, and brown adipose tissue (BAT) activity in female Syrian hamsters (Mesocricetus auratus). BAT function was assessed by measuring sympathetic nervous system (SNS) activity in BAT (estimated by the rate of norepinephrine (NE) turnover), BAT mitochondrial content (estimated by cytochrome c oxidase activity), and BAT mitochondrial proton conductance (estimated by guanosine-5'-diphosphate (GDP) binding to isolated BAT mitochondria). Food intake and body weight were both increased in short photoperiod-housed hamsters (8-hr light, 16-hr dark; LD 8:16) when compared to those of the long photoperiod-housed controls (LD 16:8). The weight gain was entirely due to an increase in carcass lipid. Interscapular BAT (IBAT) pads from short photoperiod-housed hamsters were 53% heavier and contained comparably more protein and DNA. Short photoperiod produced a 118% increase in BAT cytochrome c oxidase activity and a 41% increase in specific mitochondrial GDP binding. Whether expressed per mg wet tissue or per pad, neither the endogenous concentration of NE nor its rate of turnover were changed by short photoperiod exposure. These results demonstrate a dissociation of BAT thermogenesis from SNS activity in BAT from short photoperiod-housed Syrian hamsters.

Topics: Acclimatization; Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Circadian Rhythm; Cricetinae; Electron Transport Complex IV; Female; Guanosine Diphosphate; Light; Lipid Metabolism; Mesocricetus; Myocardium; Norepinephrine; Sympathetic Nervous System

In Experiment 1, highly significant changes were observed over the estrous cycle in body weight gain, but not in food intake, daytime resting oxygen consumption or brown fat thermogenesis in Syrian hamsters. In Experiments 2 and 3, body weight and composition, food intake, resting oxygen consumption, and brown fat thermogenesis were measured following estradiol or estradiol plus progesterone treatment in ovariectomized hamsters. The significant changes in body weight could not be explained by changes in food intake, and were not accompanied by significant alterations in daytime oxygen consumption or brown fat thermogenic activity. In Experiment 4, resting oxygen consumption and body weight were measured every 6 hours over the estrous cycle. There was a striking absence of the usual nocturnal peak in resting oxygen consumption on the night of estrus (the night of the largest body weight gain). However, brown fat thermogenic activity did not differ among groups of hamsters killed on different nights of the estrous cycle. Estradiol-induced changes in energy storage may be mediated by changes in the daily rhythm of energy expenditure which are not dependent on alterations in brown fat thermogenesis.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Circadian Rhythm; Cricetinae; Electron Transport Complex IV; Energy Metabolism; Estradiol; Estrus; Female; Guanosine Diphosphate; Mesocricetus; Mitochondria; Organ Size; Ovariectomy; Oxygen Consumption; Progesterone

Myopathic Syrian hamsters (BIO 14.6) have less brown adipose tissue (BAT) than normal. The trophic response of this tissue to cold is smaller than normal and trophic responses to diet and to photoperiod are absent. The objective was to find out whether activity of thyroxine 5'-deiodinase in their BAT was increased normally in response to cold and thus whether a defect in endogenous production of 3,5,3'-triiodothyronine might underlie the attenuated trophic response. The effect of feeding a high-fat diet on activity of 5'-deiodinase was also studied. Cold acclimation increased thyroxine 5'-deiodinase activity in BAT of the myopathic hamster, but the total remained smaller than normal because of the smaller size. The cold-induced increase in concentration of mitochondrial uncoupling protein was also smaller than normal. The level of serum 3,5,3'-triiodothyronine was low in myopathic hamsters and remained lower than normal when they were cold-exposed or cold acclimated. Feeding the high-fat diet to myopathic hamsters resulted in a greater than normal suppression of thyroxine 5'-deiodinase activity than in normal hamsters; the normal increases in protein content and in concentration of mitochondrial uncoupling protein were absent. We conclude that the defective trophic response of BAT of the myopathic hamster is not secondary to defective regulation of its thyroxine 5'-deiodinase activity because this activity does not appear to be obligatorily linked to hypertrophy of BAT. The low level of serum 3,5,3'-triiodothyronine in the myopathic hamster may be secondary to reduced capacity for peripheral thyroxine deiodination in its BAT.

Topics: Acclimatization; Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Carrier Proteins; Cold Temperature; Cricetinae; Dietary Fats; Guanosine Diphosphate; Iodide Peroxidase; Ion Channels; Male; Membrane Proteins; Mesocricetus; Mitochondria; Mitochondrial Proteins; Muscular Dystrophy, Animal; Triiodothyronine; Uncoupling Protein 1

Lactation in the rat is marked by extreme hyperphagia. The present study examined the possibility that elevated prolactin levels contribute to this increase. It also evaluated the effects of hyperprolactinemia on brown adipose tissue and carcass composition. Virgin Osborne-Mendel rats were made hyperprolactinemic via ectopic pituitary transplants (PIT, n = 9) or were sham-operated (SHAM, n = 8). Eight lactating rats (LACT) served as additional controls. Food intake, body weight and rectal temperature were recorded daily. Eleven days postsurgery (or 11-12 days postpartum), the rats were sacrificed, and brown fat (scapular, axillary, cervical and thoracic) was excised, weighed, and assayed for GDP binding, one indicator of thermogenic capacity. Carcasses were subjected to body composition analysis. Although prior to surgery, PIT and SHAM rats weighed the same, PIT rats gained significantly more weight during the experiment than did SHAMs. Percent body fat and food intake (both total intake and intake relative to metabolic body size) were significantly elevated in the PIT rats. GDP binding in both PIT and LACT rats was significantly less than in SHAMs. This was true whether GDP binding was expressed per mg mitochondrial protein or per total amount of mitochondrial protein recovered. These data confirm that brown fat thermogenic capacity is suppressed during lactation. They also demonstrate that elevations of serum prolactin, to levels that are well within physiological limits, are capable of stimulating food intake and white fat deposition in the female rat. It is presently unclear whether these results are a direct or an indirect effect of hyperprolactinemia.

Topics: Adipose Tissue, Brown; Animals; Body Composition; Body Temperature; Body Weight; Feeding Behavior; Female; Guanosine Diphosphate; Hyperprolactinemia; Lactation; Mitochondria; Pregnancy; Progesterone; Rats

Amphetamine, diethylpropion and mazindol were administered to rats in both acute and chronic experiments to measure the changes in purine nucleotide (GDP) binding to the mitochondria from interscapular brown adipose tissue. There was a dose-dependent response to acute treatment with mazindol, but no such effect with diethylpropion. The effects of mazindol and amphetamine were present as early as 3 hours after treatment, and persisted for at least 48 hours, when compared to vehicle-injected rats when all rats were fasted from the time of injection until study. There was no effect when these drugs were added in vitro to mitochondria from brown adipose tissue. Diethylpropion had no effect on GDP binding either in vivo or in vitro at any of the times tested. Following 11 days of treatment with diethylpropion, amphetamine or mazindol, there was a significant increase in purine nucleotide (GDP) binding to mitochondria only in the amphetamine-treated animals. There was no difference in body weight or food intake with any of the three drugs after the third day of chronic treatment. The differences between the effects of these three drugs and those of fenfluramine are discussed in terms of their different central mechanisms of action.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Dextroamphetamine; Diethylpropion; Dose-Response Relationship, Drug; Female; Guanine Nucleotides; Guanosine Diphosphate; Indoles; Mazindol; Mitochondria; Rats; Rats, Inbred Strains

The effects of treatment with fenfluramine or electrolytic lesions in the lateral hypothalamus (LH) on binding of guanosine 5-diphosphate (GDP) by mitochondria from brown adipose tissue have been compared in 4 experiments. In 2 experiments the lesions were lateral to the anterior hypothalamic nucleus and in the other two they were lateral to the ventromedial hypothalamic nucleus. Binding of GDP to mitochondria was significantly increased 18 hours after an electrolytic lesion in either LH site. d,1-Fenfluramine, 20 mg/kg, also increased GDP binding in both acute experiments. In the other 2 experiments GDP binding was measured 11 days after the LH lesion or after 11 daily injections of fenfluramine. When the chronic lesions were lateral to the VMN, there was a transient drop in food intake and body weight. With more anterior lesions, body weight remained significantly lower than in sham-operated rats although food intake returned slowly to control levels. Fenfluramine-treated rats had lower body weights in both chronic experiments even after food intake returned to normal. GDP-binding to mitochondria from interscapular brown adipose tissue was elevated in both of the chronically-treated fenfluramine groups but was only increased in the LH-lesioned rats whose body weight remained below normal.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Female; Fenfluramine; Guanine Nucleotides; Guanosine Diphosphate; Hypothalamic Area, Lateral; Mitochondria; Proteins; Rats

The effects of unilateral surgical denervation on brown adipose tissue (BAT) composition were evaluated to assess the importance of the sympathetic innervation in the maintenance of a high concentration of the uncoupling protein thermogenin in cold-acclimated (CA) mice and to assess whether suppression of neural activity could account for BAT atrophy observed during fasting or when CA mice are returned to a thermoneutral environment (33 degrees C). Denervation-induced BAT atrophy was characterized by protein and thermogenin losses in absence of changes in the tissue cellularity (DNA content). There was a marked reduction in the concentration of thermogenin in mitochondria isolated from denervated BAT, but the concentration of the adenine nucleotide translocator was unchanged. Fasting or exposure of CA mice to 33 degrees C induced a rapid and extensive loss of tissue protein from both innervated and denervated BAT. In CA mice exposed to 33 degrees C, there was also reduction in tissue cellularity and loss of thermogenin from BAT mitochondria. Since surgical denervation suppressed BAT hyperplasia and the increase in the mitochondrial concentration of thermogenin observed during cold exposure, these results indicate that an intact innervation is required for both synthesis and maintenance of a high mitochondrial content of thermogenin in CA mice. In addition, the lesser changes in tissue composition caused by denervation compared with those caused by fasting or exposure of CA mice to 33 degrees C question the importance of the suppression of neural activity as the exclusive cause of rapid BAT atrophy in mice.

Topics: Acclimatization; Adipose Tissue, Brown; Animals; Body Weight; Carrier Proteins; Cold Temperature; Denervation; Guanosine Diphosphate; Ion Channels; Kinetics; Male; Membrane Proteins; Mice; Mitochondria; Mitochondrial Proteins; Norepinephrine; Time Factors; Uncoupling Protein 1

The effects of a lowered rearing temperature on body weight, core temperature (Tc) and norepinephrine(NE)-stimulated thermogenesis were investigated in 16- to 17-day-old Zucker rat pups. 16-day-old fatty pups were significantly heavier (9%) than lean littermates in litters reared at 18 degrees C ("cold-reared") but not in litters reared at 25 degrees C ("normally-reared"). After 2 h isolation at 25 degrees C, Tc of lean pups was slightly higher (37.1 degrees C) in cold-reared litters than in normally-reared litters (36.4 degrees C), while fatty pups reared at either temperature were severely hypothermic (Tc = 33 - 34 degrees C). At an ambient temperature of 25 degrees C Tc in fatty and lean cold-reared pups increased to 39.5 degrees C after subcutaneous injection of 800 micrograms/kg NE. Normally-reared lean pups reached the same peak Tc after NE injection, while their fatty littermates reached a significantly lower peak Tc of 38.4 degrees C. The hypothermia associated with the onset of excess fat deposition in suckling fatty Zucker rats is not caused by a reduced capacity for NE-stimulated thermogenesis.

Topics: Adipose Tissue, Brown; Animals; Body Temperature; Body Temperature Regulation; Body Weight; Cold Temperature; Guanosine Diphosphate; Norepinephrine; Obesity; Rats; Rats, Zucker

This experiment examined the effects of diet and photoperiod on food intake, body weight, and brown adipose tissue (BAT) activity in female Siberian hamsters (Phodopus sungorus sungorus). BAT function was assessed by measuring both the sympathetic nervous system activity of BAT [estimated by the rate of norepinephrine (NE) turnover] and BAT thermogenic activity (estimated by GDP binding to BAT mitochondria). Nineteen weeks of high-fat feeding in long photoperiod [16:8 light-dark cycle (LD)] caused a 20% increase in food intake but did not affect body weight. Both NE turnover rate and GDP binding in interscapular BAT (IBAT) were increased four- to eightfold relative to that from chow-fed controls. Thus it appears that in Siberian hamsters BAT can serve the same energy-dissipating function during diet-induced overeating previously established in rats and mice. Nineteen-week exposure to a short photoperiod (LD 8:16) produced a reduction in body weight but did not affect food intake. Both NE turnover rate and GDP binding in IBAT were increased two- to fourfold relative to that from long-photoperiod controls. Thus it appears that in Siberian hamsters the photoperiod-induced improvements in thermogenic capacity are mediated via the same mechanisms as are cold- or diet-induced thermogenesis.

Topics: Adipose Tissue, Brown; Animals; Body Composition; Body Weight; Cricetinae; Dietary Fats; Eating; Female; Guanine Nucleotides; Guanosine Diphosphate; Light; Norepinephrine; Organ Size; Periodicity

The present study was carried out to investigate the effects of exercise training on energy balance in male rats acclimated at two different environmental temperatures. Sedimentary and exercised rats were housed and trained at either 24 or 4 degrees C, with the training program consisting of running on a motor-driven treadmill within their respective environments. After 45 days, energy, protein, and fat contents of rats were determined together with the energy content of food and feces. The results show that metabolizable energy intake was reduced by 10% in exercise-trained groups. Substantial differences in energy gains were observed between sedentary and trained rats; sedentary rats showed almost three times more energy gain than trained rats. Carcass analysis revealed the energy gain differences to be mainly due to varied amounts of fat deposition. Energy expenditure (kJ) excluding the cost of exercise training was corrected for metabolic body size (BW 0.75), which in turn showed no significant differences between trained rats and their respective sedentary controls. The present results suggested that exercise training in rats leads to neither increase nor decrease in energy expenditure through components additional to physical activity. The present results also indicated that brown adipose tissue thermogenesis, as assessed through mitochondrial guanosine 5'-diphosphate binding, was not significantly modified by exercise training, regardless of the temperature at which the rats were housed and trained.

Topics: Acclimatization; Adipose Tissue; Adipose Tissue, Brown; Animals; Body Weight; Eating; Energy Metabolism; Guanosine Diphosphate; Male; Mitochondria; Physical Conditioning, Animal; Proteins; Rats; Temperature

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.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Dietary Carbohydrates; Dietary Fats; Energy Intake; Food; Food Deprivation; Guanine Nucleotides; Guanosine Diphosphate; Male; Mitochondria; Rats; Rats, Inbred Strains; Sodium-Potassium-Exchanging ATPase

The effect of cold-adaptation was investigated on the brown adipose tissue of Djungarian hamsters. Animals maintained at 23 degrees C and 16 hours light per day (controls) were exposed to 5 degrees C. The wet weight of the total brown fat is reduced by some 40% within 4 days of cold-exposure, as a result of extensive triacylglycerol depletion of the tissue with no reduction in DNA; the tissue mass remains constant under persistent cold influence. The total amount of tissue mitochondria is doubled by 24 h and increases by a factor of 3 under persistent cold-stimulus, the specific respiratory capacity of the organelles remaining unchanged. The amount of 32 kDa regulatory protein per mg mitochondrial protein quantified from high-affinity GDP-binding, is increased by a factor of 2.7 after 21 days of cold-adaptation; a 9-fold increment is found of the total mitochondrial GDB-binding capacity. Comparison of nonshivering thermogenesis and the maximal thermogenic capacity of brown fat, estimated from the maximal respiration of the isolated mitochondria and the total amount of mitochondria in the tissue, suggests that brown fat may contribute about 20% to the whole-body nonshivering thermogenesis in warm-adapted controls and 45% in cold-adapted hamsters. The estimated increase in thermogenic capacity of the tissue in response to 21 days of cold-adaptation corresponds to the increase in nonshivering thermogenesis, suggesting a central thermoregulatory role of brown fat during cold-adaptation.

Topics: Acclimatization; Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Cold Temperature; Cricetinae; Guanosine Diphosphate; Mitochondria; Proteins; Time Factors

The objectives of this study were to evaluate the rate at which brown adipose tissue (BAT) from mice atrophies when its thermogenic activity is suppressed during fasting or exposure to a thermoneutral environment (33 degrees C) and whether such atrophy is accompanied by loss from BAT mitochondria of "thermogenin," the GDP binding protein associated with the calorigenic proton conductance pathway. Atrophy of mouse BAT was characterized by rapid loss of protein but unchanged tissue DNA content. The rate of protein loss varied from 2 to 6 mg protein/day depending on the environmental and feeding status of the mice. In synchrony with tissue protein loss, there was a marked reduction in the tissue content of mitochondrial proteins and of thermogenin, measured by immunoassay. However, the concentration of thermogenin in isolated mitochondria was unchanged by fasting or exposure of the mice to 33 degrees C for 48 h. By contrast, marked reduction in [3H]GDP binding to isolated mitochondria were observed after exposure of the mice to 33 degrees C. Mice acclimated at 4 but not those acclimated at 21 degrees C showed reduction in GDP binding to isolated mitochondria during fasting. These results clearly indicate that changes in purine nucleotide binding to isolated mitochondria can occur in the absence of changes in the mitochondrial concentration of thermogenin. Thus rapid decrease in BAT thermogenic capacity (e.g., during fasting or 33 degrees C exposure) appears dependent on extensive loss of tissue protein, probably whole mitochondria, rather than rapid and selective removal of thermogenin from the mitochondria.

Topics: Acclimatization; Adipose Tissue, Brown; Animals; Atrophy; Body Temperature; Body Weight; Carrier Proteins; DNA; Enzyme-Linked Immunosorbent Assay; Fasting; Guanosine Diphosphate; Immunodiffusion; Ion Channels; Male; Membrane Proteins; Mice; Mitochondria; Mitochondrial Proteins; Oxygen Consumption; Proteins; Temperature; Uncoupling Protein 1

Restricting the food intake of the genetically obese (ob/ob) mouse is known to ameliorate its cold intolerance. Cold intolerance of the ob/ob mouse is associated with defective thermogenesis in its brown adipose tissue. The objective of the experiments was to find out whether food restriction could increase the thermogenic function of brown adipose tissue of the ob/ob mouse. Obese and lean mice were fed a restricted amount of chow in one meal per day for 3-7 mo. Both lean and ob/ob mice were torpid (rectal temperature of approximately 32 degrees C) in the early morning and aroused spontaneously to a normal body temperature before the anticipated meal time. Obese mice were also torpid during the dark phase, whereas lean mice were active and had a normal body temperature at this time. Brown adipose tissue was in a thermogenically inactive state (low level of mitochondrial GDP binding) in torpid lean and ob/ob mice but became thermogenically active (increase in mitochondrial GDP binding) during stimulated arousal when body temperature increased by 6-7 degrees C in 15-30 min. Ad libitum-fed ob/ob mice had a normal diurnal rhythm in a rectal temperature that was at a lower level than in lean ad libitum-fed mice. They did not raise their rectal temperatures when stimulated and no activation of brown adipose tissue thermogenesis occurred under these conditions. Food restriction increased the capacity of both lean and ob/ob mice to raise their metabolic rate in response to injection of noradrenaline, indicating an increased capacity for thermogenesis in their brown adipose tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue, Brown; Animals; Basal Metabolism; Body Temperature; Body Weight; Circadian Rhythm; Energy Metabolism; Fatigue; Female; Food Deprivation; Guanosine Diphosphate; Mice; Mice, Obese; Norepinephrine; Obesity; Triiodothyronine

We studied diet-induced thermogenesis (DIT) in cafeteria fed monosodium glutamate (MSG) and saline-treated mice. From 12 weeks of age MSG and saline-treated mice were fed a diet of either standard chow or a cafeteria diet of standard chow supplemented with chocolate or biscuits on alternate days for six weeks. There was a significant weight gain in cafeteria fed MSG-treated mice but not in cafeteria fed saline-treated mice. In cafeteria fed MSG-treated mice there was a significant increase in resting oxygen consumption. The response to exogenous norepinephrine was significantly increased in cafeteria fed saline-treated mice. The level of specific tritiated guanosine 5'-diphosphate binding to isolated mitochondrial fractions was significantly increased in both cafeteria fed MSG and saline-treated mice. It is concluded that (1) cafeteria feeding is capable of promoting DIT, within brown adipose tissue (BAT), in MSG-treated mice and (2) the mechanisms for the induction of thermoregulatory thermogenesis (TRT) and DIT are distinct since cold-induced TRT has previously been shown to be defective in MSG-treated mice.

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Diet; DNA; Energy Intake; Female; Glutamates; Guanosine Diphosphate; Lipid Metabolism; Mice; Norepinephrine; Oxygen Consumption; Proteins; Sodium Glutamate; Tumor Protein, Translationally-Controlled 1

These experiments have tested the effects of treatment with fenfluramine on the GDP-binding to mitochondria isolated from interscapular brown adipose tissue in vitro. In acute studies, the binding of GDP was significantly increased after 3, 24, and 48 hours of treatment with a single dose of 20 mg/kg of body weight. Addition of fenfluramine in vitro, however was without effect. In a dose-response study there was no significant increase with doses of 2 or 6 mg/kg but there was a significant increase at 20 mg/kg. During eleven days of treatment, food intake was initially depressed by fenfluramine (20 mg/kg) and body weight was significantly reduced. By the ninth day of treatment however, food intake had returned to control values but the body weight remained significantly lower than in the control group. The weight of interscapular brown adipose tissue was not significantly altered but binding of GDP to isolated mitochondria was increased by 55%. These studies suggest a thermogenic effect of fenfluramine on the brown adipose tissue of rats.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Dose-Response Relationship, Drug; Eating; Female; Fenfluramine; Guanine Nucleotides; Guanosine Diphosphate; In Vitro Techniques; Mitochondria; Rats; Rats, Inbred Strains; Time Factors

The food intake of sham-operated and adrenalectomized rats was measured in 12-h intervals with animals housed in either alternating periods of 12:12 light-dark or in continuous light. The food intake with alternating light and dark was unaffected by adrenalectomy. The maintenance of a constant infusion of corticosterone in adrenalectomized rats also did not disturb the pattern of food intake. In continuous light, food intake was not significantly different in each 12-h period of the daily cycle. Neither adrenalectomy nor the injection of corticosterone, 240 micrograms/day, altered the average 12-h food intake in rats in constant light. The weight of interscapular brown adipose was smaller in adrenalectomized animals, but the protein content was unaffected. Adrenalectomy significantly increased the specific binding of the purine nucleotide GDP to mitochondria from brown adipose tissue. This specific binding was restored to normal by either corticosterone infusion or injection. We conclude that light is the principal entrainer for the average food intake during 12-h periods and that within the framework of these experiments corticosterone plays an insignificant role in controlling food intake. However, adrenalectomy did significantly increase the purine nucleotide binding to mitochondria from brown adipose tissue.

Topics: Adipose Tissue, Brown; Adrenalectomy; Animals; Body Weight; Circadian Rhythm; Corticosterone; Eating; Guanosine Diphosphate; Light; Male; Mitochondria; Rats; Rats, Inbred Strains; Time Factors

In order to investigate the possible existence of a 'masked' (i.e. non-GDP-binding) form of thermogenin (the brown-adipose-tissue specific, 32 000 Da so-called "uncoupling" protein), rats were fed a routine pellet diet or, in addition to this, a cafeteria diet. Brown-adipose-tissue mitochondria isolated from the cafeteria-fed animals showed as expected an increased (3H)GDP binding capacity (from 0.26 to 0.41 nmol/mg protein; an increase of 57%). However, when analysed by a quantitative enzyme-linked immuno-assay system for thermogenin, the mitochondria also showed an increased content of thermogenin (from 14.9 to 20.5 micrograms per mg; an increase of 38%). The ratio between thermogenin and GDP binding was 61 000 and 53 000 g/mol in the two cases; these values were not significantly different and were in good agreement with suggestions that thermogenin binds 1 GDP per thermogenin dimer. It was concluded that under the conditions investigated, there was no reason to assume the existence of a masked form of thermogenin.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Carrier Proteins; Diet; Enzyme-Linked Immunosorbent Assay; Female; GTP-Binding Proteins; Guanine Nucleotides; Guanosine Diphosphate; Humans; Ion Channels; Membrane Proteins; Mitochondria; Mitochondrial Proteins; Organ Size; Rats; Rats, Inbred Strains; Receptors, Cell Surface; Uncoupling Protein 1

Lean littermates of the genetically obese (ob/ob) mouse of confirmed genotype, +/+ wildtype or ob/+ heterozygous, were fed either stock diet or a high-energy 'cafeteria' diet. Body weights food consumption, and weights and metabolic parameters of the interscapular and dorso-cervical brown adipose tissue sites were examined. Both genotypes showed similar characteristics of food intake and body weight gain on the cafeteria diet. The ob/+ brown adipose tissue was, however, different from the +/+ in that the GDP binding to the mitochondria was lower and the cytoplasmic density of the mitochondria in the tissue was higher in both stock and cafeteria fed groups. It is suggested that the decreased GDP binding is partly compensated for by an increase in the mitochondrial content of the brown adipose tissue of the ob/+ mice, thus normalizing the total thermogenic capacity and allowing the maintenance of lean body weight despite a slight expression of the obese gene in the thermogenic pathway.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Diet; Electron Transport Complex IV; Genotype; Guanosine Diphosphate; Mice; Mice, Obese; Mitochondria

The effect of adrenalectomy on CNS myelin accumulation was investigated to determine whether glucocorticoids play a role in regulating myelination. When 14-day-old rats were adrenalectomized and sacrificed 7-8 days later, the amount of bulk-isolated myelin in whole brain, as expressed per gram wet weight of brain or per milligram DNA-phosphate, was reduced to about 75% that of sham-operated controls. Both brain weight and DNA content were unchanged by adrenalectomy. Examination of individual brain regions also revealed decreased amounts of myelin in adrenalectomized animals. Brain glycerol 3-phosphate dehydrogenase specific activity was reduced in adrenalectomized animals to 40-60% that of controls, and serum corticosterone levels were less than 0.6% of control levels. The amount of cerebral myelin in animals adrenalectomized on day 21 and sacrificed 9 days later was not significantly reduced. This suggests a possible role of glucocorticoids during the early period of rapid myelination.

Topics: Adrenalectomy; Age Factors; Animals; Body Weight; Brain; Central Nervous System; Guanosine Diphosphate; Myelin Sheath; Organ Size; Rats; Rats, Inbred F344

Experiments were performed to investigate the effect of age and genotype on brown adipose tissue thermogenesis in Zucker rats. Specific [3H]GDP binding to interscapular brown adipose tissue mitochondria ( IBATM ) was reduced in 14-day-old preobese fa/fa rats and remained lower after weaning. A gene-dosage effect of the recessive fa gene was observed in 8- to 10-wk-old rats in both IBATM [3H]GDP binding and the thermic effect of a balanced meal (50 kJ Complan ), measured by indirect calorimetry. In each case the heterozygote (Fa/fa) group had a value intermediate between those of obese (fa/fa) and the homozygous lean (Fa/Fa) groups. Norepinephrine increased IBATM [3H]GDP binding to similar levels in lean (Fa/fa) and obese (fa/fa) rats and induced similar increases in oxygen consumption in Fa/Fa, Fa/fa, and fa/fa rats. It is concluded that the impaired, diet-related brown adipose tissue thermogenesis is closely related to the primary gene defect in the obese rat. This defect may result from misregulation of the autonomic nervous system.

Topics: Adipose Tissue; Adipose Tissue, Brown; Aging; Animals; Body Temperature; Body Temperature Regulation; Body Weight; Diet; Energy Intake; Genotype; Guanosine Diphosphate; Mitochondria; Norepinephrine; Oxygen Consumption; Rats; Rats, Zucker

The effect of acclimation temperature on the concentration of the mitochondrial 'uncoupling' protein (Mr 32000) from brown adipose tissue of mice has been investigated. The uncoupling protein was measured by a specific radioimmunoassay. Between 33 degrees C (thermoneutrality) and -2 degrees C there was a progressive increase with decreasing environmental temperature in the amount of uncoupling protein. For mice at -2 degrees C the mitochondrial concentration of the protein was 9-times higher than at 33 degrees C, while the total amount of the protein in interscapular brown adipose tissue was estimated to be nearly 80-times greater at -2 degrees C compared to 33 degrees C.

Topics: Acclimatization; Adipose Tissue, Brown; Animals; Body Weight; Carrier Proteins; Electron Transport Complex IV; Guanosine Diphosphate; Ion Channels; Male; Membrane Proteins; Mice; Mice, Inbred Strains; Mitochondria; Mitochondrial Proteins; Radioimmunoassay; Temperature; Uncoupling Protein 1

Topics: Animals; Body Weight; Cytochrome P-450 Enzyme System; Food Deprivation; Guanosine Diphosphate; Hexobarbital; Malate Dehydrogenase; Male; Microsomes, Liver; NADP; Organ Size; Rats; Sleep

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Diet; Energy Metabolism; Guanosine Diphosphate; Humans; Hyperphagia; Norepinephrine; Rats; Sodium-Potassium-Exchanging ATPase; Sympathetic Nervous System

Reports on a reciprocal relationship between sympathetic-nerve and experimentally induced changes in thyroid-hormone activity called into question the proposed role of thyroxine in the changes seen in the brown fat after cold adaptation. Rats reared at +30, +22, and +5 degrees C received daily injections of thyroxine (1 mg/kg). After 3 wk of treatment, the thermogenic state of the tissue was assessed by measuring the capacity of the brown fat mitochondria to bind guanosine 5'-diphosphate (GDP). GDP-inhibited mitochondrial swelling, brown adipose tissue (BAT) wet weights, and mitochondrial yields were also measured. The control animals showed a linear increase in GDP binding between +30 and +5 degrees C. Thyroxine was found to lower the GDP binding markedly at +5 degrees C, less so at +22 degrees C, while no effect was evident at +30 degrees C. The values at +22 and +30 degrees C were identical. The other parameters studied all confirmed these results. The conclusion made is that the thyroxine-induced rise in basal metabolic rate lowers the critical temperature and reduces the demand for nonshivering thermogenesis. This is reflected in the reduced GDP binding and hence heating capacity of the brown fat mitochondria.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Female; Guanine Nucleotides; Guanosine Diphosphate; Kinetics; Mitochondria; Mitochondrial Swelling; Rats; Rats, Inbred Strains; Temperature; Thyroxine

Topics: Adenosine Diphosphate; Adipose Tissue, Brown; Animals; Body Temperature Regulation; Body Weight; Cold Temperature; Electron Transport Complex IV; Guanine Nucleotides; Guanosine Diphosphate; Mice; Mice, Obese; Mitochondria