BAT Thermogenesis Research Articles

Uptake of glucose and release of fatty acids and glycerol by rat brown adipose tissue in vivo

The net in vivo uptake or release of free fatty acids glycerol, glucose, lactate, and pyruvate by the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats was determined from measurements of plasma arteriovenous concentration differences across IBAT and tissue blood flow. Measurements were made without stimulation of the tissue and also during submaximal and maximal stimulation by infused noradrenaline (NA), the physiological activator of BAT thermogenesis. There was no appreciable uptake of glucose or release of fatty acids and glycerol by the nonstimulated tissue. At both levels of stimulation there was significant uptake of glucose (1.7 and 2.0 mumol/min) and release of glycerol (0.9 and 1.2 mumol/min), but only at maximal stimulation was there significant release of fatty acids (1.9 mumol/min). Release of lactate and pyruvate accounted for 33% of the glucose taken up at submaximal stimulation and 88% at maximal stimulation. By calculation, the remainder of the glucose taken up was sufficient to have fueled about 12% of the thermogenesis at submaximal stimulation, but only about 2% at maximal stimulation. As estimated from the rate of glycerol release, the rate of triglyceride hydrolysis was sufficient at submaximal stimulation to fuel IBAT thermogenesis entirely with the resulting fatty acids, but it was not sufficient to do so at maximal stimulation when some of the fatty acid was exported. It is suggested that at maximal NA-induced thermogenesis a portion of lipolysis proceeded only to the level of mono- and di-glycerides with the result that glycerol release did not fully reflect the rate of fatty acid formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Weight loss induced by chronic phenylpropanolamine: anorexia and brown adipose tissue thermogenesis.

The effects of chronic treatment with phenylpropanolamine (PPA) on body weight (BW), food intake (FI), and water intake (WI) and interscapular brown adipose tissue (IBAT) thermogenesis in adult male Sprague-Dawley rats were evaluated in 2 experiments. In Experiment 1, rats were treated (IP) twice daily (0900 and 2100 hr) for 12 days with either saline or 5, 10, or 20 mg/kg dl-PPA. Rats treated with 20 mg/kg dl-PPA exhibited significant decreases in both FI and BW but not WI. Basal IBAT temperature was slightly increased in chronic 20 mg/kg dl-PPA rats and there was no evidence of tolerance to the acute IBAT thermogenic effect of 20 mg/kg dl-PPA. In Experiment 2, rats were treated twice daily (0900 and 2100 hr) for 12 days with either saline or 20 mg/kg of either d-PPA or l-PPA. There was a 2-fold difference in the potency of these PPA isomers on FI, BW and IBAT thermogenesis. Body composition analyses revealed that l-PPA, but not d-PPA, induced a significant loss of carcass lipid without significant changes in carcass ash, water or protein levels. These data suggest that the weight-reducing action of PPA may reflect a combined effect of this drug on both food intake and BAT thermogenesis.

Effects of guanethidine sympathectomy on feeding, drinking, weight gain and amphetamine anorexia in the rat

Adult female rats that underwent sympathectomy induced by guanethidine treatment (10, 20 or 40 mg/kg) exhibited markedly increased water intake, but did not display significant alterations of either food intake, body weight, or the Lee Index of obesity. Guanethidine treatment did not attenuate amphetamine anorexia as evidenced by comparable dose-dependent reductions in food intake to d-amphetamine sulfate (0.25, 0.50, 1.0, and 2.0 mg/kg) in sympathectomized and control rats. These data are not consistent with the hypothesis that amphetamine anorexia is partially mediated via enhanced BAT thermogenesis.

Synergism between caffeine and dl-phenylpropanolamine on brown adipose tissue thermogenesis in the adult rat

Caffeine produces enhanced oxygen consumption, an effect that may reflect an action of caffeine on brown adipose thermogenesis. In Experiment 1, adult male rats were anesthetized with 1.2 g/kg urethane and treated (IP) with either 0.9% saline or 10, 20 or 40 mg/kg caffeine (n = 4 each group). Interscapular BAT (IBAT) and rectal temperatures were recorded every minute for 10 minutes prior to and 30 minutes following drug injection. Stable IBAT and rectal temperatures were observed prior to and after saline injection whereas rats treated with 20 and 40 mg/kg caffeine exhibited moderate increases in IBAT, but not rectal, temperature. In Experiment 2, adult male rats were treated with either 0.9% saline or 10 mg/kg caffeine, anesthetized with urethane (1.2 g/kg) and treated (30 minutes after pretreatment injections) with either 0.9% saline or 10 mg/kg dl-phenylpropanolamine (dl-PPA). A combination of caffeine and dl-PPA produced significantly greater BAT thermogenesis than just dl-PPA alone. The implications of these data for the inclusion of caffeine in over-the-counter diet-pills are discussed.

Brown adipose tissue after ventromedial hypothalamic lesions in rats.

The interscapular brown adipose tissue (IBAT) from obese rats with lesions of the ventromedial hypothalamus (VMH) was approximately 5 times heavier than those from controls. This hypertrophy of IBAT was associated with a marked enlargement of constituent adipocytes and their apparent transformation from multiloculated structure of lipid droplets into the uniloculated structure. The rate of fatty acid synthesis in IBAT of the obese rats was less than one-tenth of that in control rats and approximated the value in white adipose tissue (WAT) when they were starved for 24 h. When rats were fed, the synthetic rate was increased, but the lipogenic response of IBAT in the obese rats was much greater than that in controls, the extent of the response being comparable to that of WAT. The IBAT temperature rose rapidly on electrical stimulation of the sympathetic nerves to the tissue in control rats, whereas the temperature response was reduced markedly in the obese rats. It was suggested that thermogenesis in BAT was impaired in obese rats with VMH lesions by decreasing triglyceride turnover in BAT, probably due to dysfunction of the sympathetic nervous system and a consequent transformation of BAT into WAT.

Effects of surgical removal of interscapular brown adipose tissue on food intake and amphetamine anorexia

Adult male albino rats underwent surgical removal of interscapular brown adipose tissue (IBATX) or sham surgery. After recovery from surgery, daily 60-min feeding tests were conducted to evaluate the potential effect of IBATX on amphetamine anorexia. d-Amphetamine sulfate, at 1.0, 2.0, and 4.0 mg/kg (ip), induced dose-dependent but comparable anorexia in both IBATX and sham-surgery control rats. The implications of these data for the notion that amphetamine induces satiety, in part, via stimulation of BAT thermogenesis are discussed.

Defective brown adipose oxygen consumption in obese Zucker rats.

The thermogenic capacity and morphologic characteristics of interscapular brown adipose tissue (IBAT) were assessed in 3- to 4-mo-old male, lean and obese Zucker rats. Pads from obese rats were threefold heavier and contained similar numbers of cells but an average of 50% fewer multilocular cells than pads from lean rats and 40% less mitochondrial protein per pad. The maximal number of beta-adrenoreceptor binding sites, as assessed by [125I]iodocyanopindolol binding to isolated brown adipocytes from obese rats was 50% of that in lean rats on a per cell and per pad basis. Basal and norepinephrine (NE)-stimulated in vitro oxygen consumption in isolated brown adipocytes from lean rats correlated directly with the proportion of mutilocular cells present. This correlation was not seen in cells from obese rats that had a 50% decrease in their basal respiratory rates and could not be further stimulated by excess NE or fatty acid. Electron micrographs of IBAT from obese rats revealed distorted mitochondrial shapes and cristae patterns and the presence of numerous inclusion bodies. Because NE-stimulated lipolysis had previously been shown to be normal in the obese Zucker rat, these data suggest that defective BAT thermogenesis in the obese rat is due to an inability of mitochondria to utilize free fatty acids for the production of enhanced oxygen consumption.

Baroreflex suppression on non-shivering thermogenesis in restrained and non-restrained rats

1. 1. An increase in the aortic blood pressure (BP) at 13°C decreased heat production ( M) and brown adipose tissue temperature ( T BAT) in unanaesthetized rats. 2. 2. The increase in BP failed to produce these changes in the rats after denervation of the sinoaortic baroreceptors, but not after premedication with atropine. 3. 3. Physical restraint attenuated the fall in T BAT. 4. 4. These results indicate that BAT thermogenesis is suppressed by the sinoaortic-baroreceptor reflex in unanaesthetized rats.

Decreased rate of fatty acid synthesis in brown adipose tissue of hypothalamic obese rats

Obese rats with lesions of the ventromedial hypothalamus (VMH) exhibited a 3-fold increase in the wet weight of interscapular brown adipose tissue (IBAT), due to an incresed triglyceride content, compared with lean controls. The rate of lipogenesis in IBAT was much higher than that in white adipose tissues in control rats, but decreased greatly in rats with VMH lesions and approximated the value in white adipose tissues. It was suggested that thermogenesis in BAT was impaired after VMH lesions by decreasing triglyceride turnover in BAT.

Ontogenesis of brown adipose tissue thermogenesis in the rabbit

Basal and norepinephrine (NE) stimulated oxygen consumption was measured in BAT cells isolated from fetal and newborn rabbits at 24, 28, and 31 days gestation, and 3 and 10 days postnatal age. Maximum catecholamine stimulated respiration was measured at a final NE concentration of 10 −6 M. Cell diameter, calculated cell volume and mitochondrial alpha glycerophosphate dehydrogenase (αGPD) were also determined at each age. Basal respiration increased continuously during fetal and neonatal life from a mean (±SEM) of 12.2 ± 0.4 μl O 2/10 6 cells · hr at 24 days gestation to a mean of 70.5 ± 4.2 μl O 2/10 6 cells · hr at 10 days of age. Stimulated respiration increased primarily during fetal development from a mean of 53.7 ± 3.4 μl O 2/10 6 cells · hr at 24 days gestation to 670.5 ± 60.4 μl O 2/10 6 cells · hr at 31 days. A further increase of 30% measured at 10 days of age was also observed. BAT mitochondrial αGPD activity was several fold greater than that measured in liver. Both cell size and enzyme activity increased in parallel to increasing respiratory response to NE. We conclude from this data that the maturation of catecholamine stimulated BAT thermogenesis occurs primarily in the fetus prior to delivery. This increase is associated with both an increase in mitochondrial enzyme activity and an increase in cell size.