The impact of increased dietary lipid on the regulation of glucose uptake and oxidation by insulin in brown- and a range of white-adipose-tissue depots in vivo.

OBJECTIVE: To determine: (a) whether active pyruvate dehydrogenase (PDHa) activity in interscapular brown adipose tissue (IBAT) is acutely regulated by altered insulin status at euglycaemia; (b) the relationship between glucose uptake/phosphorylation and PDHa activities in IBAT in vivo; and (c) the impact of increased dietary lipid on the regulation of glucose uptake and oxidation by insulin in IBAT in comparison with that exerted on various white adipose tissue depots. DESIGN: Rats were provided with either a standard diet (8% fat, 72% carbohydrate, by energy) or a diet moderately high in saturated fat (47%, by energy) and low in carbohydrate (33%, by energy) for four weeks. Rats were studied in the absorptive state, in the post-absorptive state or after 2.5 h euglycaemic hyperinsulinaemia. Tissues sampled included IBAT and four white adipose tissue depots, two abdominal (parametrial (PM) and perirenal (PR)) and two superficial (subcutaneous (SC) and interscapular (IS)). MEASUREMENTS: Whole-body glucose disposal was estimated using [3-3H]glucose. Glucose uptake/phosphorylation in vivo was estimated using 2-deoxy[1-3H]-D-glucose. Insulin action was evaluated using the euglycaemic-hyperinsulinaemic clamp technique. PDHa activity was assayed spectrophotometrically in freeze-clamped tissue extracts. PDH kinase (PDK) activities were assayed in mitochondrial extracts by rates of ATP-dependent PDHa inactivation. RESULTS: Whole-body glucose disposal was decreased by high-fat-feeding in the post-absorptive state (P < 0.05) and during euglycaemic hyperinsulinaemia (P < 0.01). Glucose transport/phosphorylation in IBAT was decreased by high-fat feeding in the absorptive (P < 0.001) and post-absorptive states (by 84%, P < 0.05) and during steady-state euglycaemic hyperinsulinaemia (by 73%, P < 0.001). IBAT PDHa activities were suppressed by high-fat feeding. Euglycaemic hyperinsulinaemia in post-absorptive control rats increased PDHa activities in IBAT (P < 0.001) to values comparable to those found in the absorptive state. Although IBAT PDHa activities were increased by euglycaemic hyperinsulinaemia in post-absorptive high-fat-fed rats, they remained lower (by 55%; P < 0.01) than those of controls. The failure of hyperinsulinaemia to normalise IBAT pyruvate dehydrogenase complex (PDHC) activities in high-fat-fed rats was associated with a stable 1.4-fold increase in IBAT PDK activity. High-fat feeding decreased glucose utilisation rates in the post-absorptive state in IS, but not in SC, PM or PR white adipose tissue depots. Euglycaemic hyperinsulinaemia significantly increased glucose utilisation in three out of the four depots of the control rats, but did not elicit statistically-significant changes in high-fat-fed rats. High-fat feeding influenced PDHa activity in PR, but was without significant effect on PDHa activity in PM, SC and IS. CONCLUSIONS: The results demonstrate that PDHa activity in the IBAT of rats maintained on standard diet responds to changes in insulin concentrations over the low physiological range, and that inactivation of PDHa in IBAT after feeding a diet moderately high in saturated fat is a consequence of the induction of tissue insulin resistance. Effects of this dietary regime on PDHa activity are paralleled by changes in insulin-stimulated glucose uptake/phosphorylation by IBAT in vivo, and IBAT is specifically targeted, with only moderate effects in white adipose tissue. The finding of impaired activation of BAT glucose transport/phosphorylation and PDHa activity in response to insulin may contribute to impaired thermogenesis in rats maintained on diets containing a relatively high proportion of saturated fat.     

Differential activation of the sympathetic innervation of adipose tissues by melanocortin receptor stimulation

Melanocortins are implicated in the control of energy intake/expenditure. Centrally administered melanotan II (MTII), a synthetic melanocortin 3/4-receptor agonist, decreases adiposity beyond that accountable by food intake decreases. Melanocortin-4 receptor (MC4-R) mRNA is expressed on sympathetic nervous system (SNS) outflow neurons to white adipose tissue (WAT) in Siberian hamsters, suggesting a role in lipid mobilization. Therefore, we tested whether third ventricular injections of MTII increased sympathetic drive to WAT and interscapular brown adipose tissue (IBAT) using norepinephrine turnover (NETO) as a measure of sympathetic drive. We also tested for MTII-induced changes in lipolysis-related WAT gene expression (beta3-adrenoceptors, hormone sensitive lipase) and IBAT thermogenesis (beta3-adrenoceptor, uncoupling protein-1). Finally, we tested whether third ventricularly injected MTII, a highly selective MC4-R agonist (cyclo[beta-Ala-His-D-Phe-Arg-Trp-Glu]NH2) increased or agouti-related protein decreased IBAT temperature in hamsters implanted with sc IBAT temperature transponders. Centrally administered MTII provoked differential sympathetic drives to WAT and IBAT (increased inguinal WAT, dorsosubcutaneous WAT and IBAT NETO, but not epididymal WAT and retroperitoneal WAT NETO). MTII also increased circulating concentrations of the lipolytic products free fatty acids and glycerol but not plasma catecholamines, suggesting lipid mobilization via WAT SNS innervation and not via adrenal medullary catecholamines. WAT or IBAT gene expression was largely unaffected by acute MTII treatment, but IBAT temperature was increased by MTII and the MC4-R agonist and decreased by agouti-related protein. Collectively, this is the first demonstration of central melanocortin agonist stimulation of WAT lipolysis through the SNS and confirms melanocortin-induced changes in BAT thermogenesis.     

The influence of the sympathetic nervous system on brown adipose tissue: an experimental and histopathologic study on aging]

Brown adipose tissue (BAT) is known to be a principal energy source of non-shivering thermogenesis and related diet-induced thermogenesis. These regulate body temperature and body weight and are controlled by the dissipation of excessive dietary caloric intake. We carried out histopathologic, immunohistochemical and biochemical studies of BAT in rats in relation to aging changes. Four groups of Donryu strain male rats (5 each of 1 month, 2 months, 4 months and 20 months of age) were used. They had been given commercial chow and tap water ad libitum and were kept in an air-conditioned room. Body weight (BW), interscapular BAT weight (IBATW) and g IBATW/g BW of rats were measured. Nor-adrenalin (NA), and dopamine-beta-hydroxylase (DBH) of IBAT were determined. To evaluate the catecholaminergic effects of BAT, morphometric quantitation of BAT was carried out based on the cytoplasmic locularity of fat globules in the BAT cells. Distribution of DBH in BAT was assessed immunohistochemically by the avidin biotin peroxidase complex method. With the use of statistical analysis of variance procedure, there were highly significant decreases in the ratio of g IBATW/g BW (p less than 0.0001) and in the concentrations of NA (p less than 0.0001) and DBH (p less than 0.01) between young (weaning at 1 month old) rats and adult (aged from 4 to 20 months) rats. In the morphometric measurement, by the statistical analysis system (SAS) Spearman correlation coefficient method, there was a significant increase of Type 5 cell (monocular brown adipose tissue cell) in 4 month and 20 month rats, compared to 1 month and 2 month rats (p less than 0.05). Immunohistochemical study of BAT showed localization of DBH in perivascular mesenchymal cells which corresponded with the morphologic distribution of catecholamine as reported by Lever. The results suggest that in the processes of aging in the rat there are reductions in the ratio of g IBATW/g BW, NA and the activity in DBH.     

Effects of sucrose feeding and denervation on lipogenesis in brown adipose tissue

Rats were fed standard laboratory chow or sucrose + chow for 2-3 weeks. Sucrose feeding significantly increased the size and norepinephrine content of interscapular brown adipose tissue (BAT). Sucrose feeding stimulated in vivo lipogenesis in BAT, white adipose tissue, and liver. Unilateral denervation reduced BAT norepinephrine content by 90%, and significantly reduced BAT protein and DNA content. Prior surgical denervation of BAT had no effect on lipogenesis in chow-fed rats, but reduced the sucrose-induced lipogenesis in BAT by 75% and increased lipogenesis in retroperitoneal white adipose tissue of sucrose-fed rats. These data demonstrate that the optimal stimulation of lipogenesis in BAT by sucrose feeding requires innervation of this tissue.     

Neural control of the alpha-subunit of Gs messenger ribonucleic acid in rat brown adipose tissue

Neural stimulation of rat interscapular brown adipose tissue (IBAT) can greatly modify transmembrane signalling in this tissue. As part of an investigation into the molecular mechanisms of such modulation we have examined the effects of surgical denervation of BAT and cold exposure (a treatment that increases neural stimulation of BAT) on the levels of mRNA encoding for the alpha-subunit of Gs, the GTP-binding protein that regulates adenylate cyclase. The G alpha s mRNA content of BAT per unit RNA was 5-10 times greater than that of lung, liver, or caudate-putamen. Surgical denervation of BAT of warm-adapted rats reduced G alpha s mRNA content by 30% within 8 h postsurgery and by 65% by 72 h. Concurrent infusion of norepinephrine completely prevented the denervation-induced decline in G alpha s mRNA at 72 h. Infusion of the beta-adrenergic agonist isoproterenol also prevented the denervation-induced decline in G alpha s mRNA, but infusion of the alpha 1-adrenergic agonist phenylephrine was without effect. Exposing rats to 4 C for 3 days approximately doubled the level of G alpha s mRNA. Interestingly, surgical denervation did not prevent the cold-induced increase in G alpha s mRNA levels, indicating that this effect is independent of local innervation. Despite reducing G alpha s mRNA levels by about 60%, surgical denervation failed to alter the concentration of G alpha s protein in IBAT membranes of warm-adapted rats, as determined by immunoblotting. Previous work indicates that cold exposure does not increase the concentration of G alpha s in IBAT membranes. Taken with the present results, these data indicate that there is no simple relationship between tissue G alpha s mRNA content and membrane G alpha s concentration in IBAT.     

Modulation of fatty acid synthesis in vivo in brown adipose tissue, liver and white adipose tissue of cold-acclimated rats

The present experiment was an appraisal of the relative importance of fatty acid synthesis in brown adipose tissue (BAT) in young 28 or 5 degrees C adapted rats (9 weeks old). With a low-fat diet in vivo incorporation of 3H2O into BAT fatty acids was 8 times lower during the day than during the night and was not modified by a 6-hour fast during the day (28 degrees C). Cold acclimation doubled (night) or increased 8 times (day) BAT lipogenesis. Fasting led to a halving of the diurnal rate. A high-fat diet led to large decrease in synthesis rate during the night but had a weak effect on diurnal synthesis. The specific activity of fatty acids was 3 times lower in phospholipids than in neutral lipids. A comparison between 9- and 15-week-old rats indicated that in older warm-adapted rats BAT lipogenesis decreased by half but that cold stimulation was unaltered. These results were compared with hepatic and epididymal white adipose tissue lipogenesis. In conclusion, we showed that BAT of 5 degrees C rats is an important but not the major site for the conversion of carbohydrate to fat and that the proportional involvement of each tissue is age-dependent.     

Energetic responses are triggered by caudal brainstem melanocortin receptor stimulation and mediated by local sympathetic effector circuits

The central melanocortin system is a critical contributor to energy balance control. Melanocortin receptors (MC-Rs) are widely distributed throughout forebrain and caudal brainstem nuclei. To assess the contribution of hindbrain MC-Rs to the control of energy expenditure, the MC3/4R agonist melanotan II (MTII) was delivered to either the fourth ventricle or medullary raphe of neurologically intact rats and chronic decerebrate (CD) rats, and interscapular brown adipose tissue (IBAT) temperature (T(IBAT)), core temperature (T(C)), heart rate (HR), and spontaneous activity were recorded. Fourth ventricular MTII (0.1, 1.0 nmol) significantly increased T(IBAT), T(C), and HR in intact rats (T(C): +0.33 +/- 0.08, +0.41 +/- 0.09 C; HR: +40.84 +/- 7.29, +69.04 +/- 6.83 beats per minute) and in CDs (T(C): +1.39 +/- 0.67, +1.52 +/- 0.37 C; HR: +83.21 +/- 19.2, +107.38 +/- 17.65 beats per minute). Response magnitude was greater in CD rats than in neurologically intact rats. T(IBAT), T(C), and HR were significantly increased after 10 pmol MTII delivery to the medullary raphe of intact rats, and here too, the response magnitude was greater in decerebrate rats. The hyperthermia, IBAT thermogenesis, and tachycardia observed in CD rats after fourth ventricular and hindbrain parenchymal MTII injections support the hypothesis that hindbrain MC-R stimulation engages endemic circuits that link sympathetic outflows to thermogenic and cardiac effectors, and that forebrain processing and forebrain-caudal brainstem communication are not required for response production.     

Type II Thyroxine 5''-Deiodinase Activity in the Rat Brown Adipose Tissue, Pineal Gland, Harderian Gland, and Cerebral Cortex: Effect of Acute Cold Exposure and Lack of Relationship to Pineal Melatonin Synthesis

The effect of acute cold exposure for 6 hours on nocturnal type II thyroxine 5'-deiodinase (5'-D) activity was studied in brown adipose tissue (BAT), Harderian gland, cerebral cortex, and pineal gland of the rat. Moreover, the effect of iopanoic acid (IOP), a potent inhibitor of 5'-D activity, on both pineal N-acetyltransferase (NAT) activity and melatonin content in rats maintained in a cold environment was also examined. Results show that acute cold exposure significantly increases 5'-D activity in BAT but not in either the pineal gland, Harderian gland, or cerebral cortex. In all tissues, the injection of IOP reduced dramatically 5'-D activity, while exposure of the animals to light at night reduced 5'-D activity in pineal gland but not in either the Harderian gland or BAT while light exposure at night increased cerebrocortical 5'-D activity. Cold exposure did not change either pineal NAT activity or the melatonin content of the gland. Finally, when pineal 5'-D activity was inhibited by IOP treatment, neither nocturnal pineal NAT activity nor melatonin content was affected.     

Sympathetic and sensory innervation of brown adipose tissue

The innervation of brown adipose tissue (BAT) by the sympathetic nervous system (SNS) is incontrovertible and, with its activation, functions as the principal, if not exclusive, stimulator of BAT thermogenesis. The parasympathetic innervation of BAT only appears in two minor BAT depots, but not in the major interscapular BAT (IBAT) depot. BAT thermogenesis is triggered by the release of norepinephrine from its sympathetic nerve terminals, stimulating β3-adrenoceptors that turns on a cascade of intracellular events ending in activation of uncoupling protein-1 (UCP-1). BAT also has sensory innervation that may function to monitor BAT lipolysis, a response necessary for activation of UCP-1 by fatty acids, or perhaps responding in a feedback manner to BAT temperature changes. The central sympathetic outflow circuits ultimately terminating in BAT have been revealed by injecting the retrograde viral transneuronal tract tracer, pseudorabies virus, into the tissue; moreover, there is a high degree of colocalization of melanocortin 4-receptor mRNA on these neurons across the neural axis. The necessary and sufficient central BAT SNS outflow sites that are activated by various thermogenic stimuli are not precisely known. In a chronic decerebration procedure, IBAT UCP-1 gene expression can be triggered by fourth ventricular injections of melanotan II, the melanocortin 3/4 receptor agonist, suggesting that there is sufficient hindbrain neural circuitry to generate thermogenic responses with this stimulation. The recent recognition of BAT in normal adult humans suggests a potential target for stimulation of energy expenditure by BAT to help mitigate increased body fat storage.     

Impaired starvation-induced loss of mitochondrial protein in the brown adipose tissue of dietary obese rats.

The effects of fasting and refeeding on interscapular brown adipose tissue (IBAT) in normal rats and in those made obese by cafeteria feeding was investigated in order to evaluate the sequential feeding responses relating to the IBAT facultative thermogenesis. The thermogenic activity (GDP binding) and related parameters such as IBAT mass, tissue protein, mitochondrial protein and cytochrome c oxidase (COX) activity were compared in fed, fasted and refed situations in controls and in rats made obese by cafeteria feeding. The IBAT mass, tissue protein content, mitochondrial protein content, total COX activity and specific GDP binding were significantly increased by the cafeteria diet. The thermogenic response to fasting and refeeding was different between control and cafeteria obese rats. Thus, in control rats, the loss of mitochondrial protein as well as total COX activity are probably the main responses to fasting, whereas in cafeteria obese rats no changes in mitochondrial protein and total COX activity occur during fasting. Furthermore mitochondrial protein and total COX activity were not recovered during refeeding in control rats, and no changes occurred in cafeteria fed rats. However, the proton conductance pathway (measured by GDP binding) is inactivated in control and cafeteria fed rats on fasting. In conclusion, these results indicate different responses during fasting in the mitochondrial protein between control and dietary obese rats, suggesting a possible activated mitochondrial proteolysis in the control rats only.     

Opposite effects of feeding a vitamin A-deficient diet and retinoic acid treatment on brown adipose tissue uncoupling protein 1 (UCP1), UCP2 and leptin expression

The relationship between interscapular brown adipose tissue (IBAT) thermogenic potential and vitamin A status was investigated by studying the effects of feeding a vitamin A-deficient diet and all-trans retinoic acid (tRA) treatment on body weight and IBAT parameters in mice. Feeding a vitamin A-deficient diet tended to trigger opposite effects to those of tRA treatment, namely increased body weight, IBAT weight, adiposity and leptin mRNA expression, and reduced IBAT thermogenic potential in terms of uncoupling protein 1 (UCP1) mRNA and UCP2 mRNA expression. The results emphasize the importance of retinoids as physiological regulators of brown adipose tissue.     

Nocturnal increase in pineal melatonin production in two lemming species, Dicrostonyx hudsonius and D. groenlandicus

Pineal N-acetyltransferase (NAT) activity and melatonin levels and thyroxine 5'-deiodinase (5'D) activity in brown adipose tissue (BAT) were compared during the day and night in two species of lemmings, Dicrostonyx hudsonius and D. groenlandicus. In both species, NAT and melatonin exhibited significant night-time increases in the pineal gland. Thyroxine 5'D activity in BAT did not show a statistically significant day-night difference in either species of lemming, suggesting the night-time rise in melatonin does not induce a similar increase in BAT 5'D.     

Acute effects of fat and carbohydrate on metabolic rate in normal, cold-acclimated and lean and obese (fa/fa) Zucker rats

The rise in metabolic rate after intragastric feeding with fat and carbohydrate was enhanced in cold-acclimated (5 degrees C) rats and diminished in warm-acclimated (30 degrees C) rats compared to controls (24 degrees C), but the response was largest in cold-acclimated animals intubated with fat. These acute effects of nutrients were almost completely abolished by beta-adrenergic blockade with propranolol in all groups, while the parasympathetic antagonist atropine sulphate enhanced the responses in control rats, but had little effect in cold-acclimated animals. Feeding carbohydrate produced similar increases in interscapular brown adipose tissue (BAT) temperature in control and cold-acclimated rats, but fat caused a much greater rise in the latter group. The thermic effects of both nutrients were lower in genetically obese Zucker rats than in their lean littermates. Atropine slightly increased the thermic responses to fat and carbohydrate in the lean Zucker rats and caused marked potentiation in obese rats intubated with fat, but did not alter the effect of carbohydrate in the obese animals These data suggest that the size of the acute rise in metabolic rate after fat and carbohydrate is dependent on the thermogenic capacity of the animal. The response to fat was particularly large in cold-acclimated rats, where BAT activity is high, possibly due to a direct action of fat on the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms of thermogenesis induced by low protein diets

Weanling (22-day-old) rats fed a low protein (8% casein) diet consumed the same amount of energy as controls (22% casein diet), but intake corrected for body size (kJ/kg0.75) was increased in the former group. Weight gain and the efficiency of gain (g gain/MJ) were markedly reduced in low protein fed rats. Resting oxygen consumption (VO2) was elevated by 15% in the low protein group but this difference was completely abolished by beta-adrenergic blockade with propranolol. Interscapular brown adipose tissue (BAT) mass, protein content, mitochondrial yield and GDP binding were increased in low protein fed rats but mitochondrial alpha-glycophosphate shuttle activity of BAT was unaltered, although shuttle activity was elevated in liver mitochondria. Plasma triiodothyronine levels were increased by 64% in the low protein group, whereas insulin levels were markedly reduced in spite of normal blood glucose levels. Resting VO2 and BAT mass were also increased in older (55-day-old) rats fed the low protein diet, but the changes were smaller than in weanling rats. These data suggest that the decreased metabolic efficiency seen in rats fed protein deficient diets involves sympathetic activation of BAT, and is therefore similar to the thermogenic responses seen in cold adapted and cafeteria-fed animals.     

Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue

The central melanocortin 4 receptor (MC4R) plays a critical role in energy homeostasis, although little is known regarding its role in the regulation of adaptive thermogenesis of brown adipose tissue (BAT). Here we show using retrograde transsynaptic tracing with attenuated pseudorabies virus coupled with dual-label immunohistochemistry that specific subsets of MC4R-expressing neurons in multiple nuclei of the central nervous system known to regulate sympathetic outflow polysynaptically connect with interscapular BAT (IBAT). Furthermore, we show that MC4R-/- and agouti-related peptide-treated mice are defective in HF diet-induced up-regulation of uncoupling protein 1 in IBAT. Additionally, MC4R-/- mice exposed to 4 C for 4 h exhibit a defect in up-regulation of uncoupling protein 1 levels in IBAT. Our results provide a neuroanatomic substrate for MC4R regulating sympathetically mediated IBAT thermogenesis and demonstrate that the MC4R is critically required for acute high-fat- and cold-induced IBAT thermogenesis.     

Physiological difference between obese (fa/fa) Zucker rats and lean Zucker rats concerning adiponectin

Obese (fa/fa) Zucker rat is a spontaneous genetic obesity model and, by comparison with lean Zucker rat, exhibits hyperphagia, hyperinsulinemia, and hyperlipidemia. The aim of this study was to examine the physiological difference concerning adiponectin between obese (fa/fa) Zucker rats and control lean Zucker rats. We therefore measured plasma adiponectin level and analyzed adiponectin and adiponectin receptor 1 mRNA expression in retroperitoneal white adipose tissue (RT WAT), brown adipose tissue (BAT), liver, and soleus muscle. We also examined the tissue mRNA expression of peroxisome proliferator-activated receptor alpha (PPAR alpha), PPAR delta, and PPAR gamma, which regulate adiponectin expression sensitivity to a PPAR gamma agonist shown by brown adipocytes from obese (fa/fa) Zucker rats and lean Zucker rats, by measuring adiponectin release from these cells. Plasma adiponectin levels of obese (fa/fa) Zucker rats were significantly higher than those of lean Zucker rats. Adiponectin mRNA expression levels in RT WAT were lower in obese (fa/fa) Zucker rats than in lean Zucker rats, but those in BAT were higher. Adiponectin receptor 1 expression levels in RT WAT, BAT, and liver of obese (fa/fa) Zucker rats were lower than in lean Zucker rats. The expression level of PPAR alpha, PPAR delta, and PPAR gamma in BAT was lower in obese (fa/fa) Zucker rats than in lean Zucker rats. Moreover, the PPAR gamma agonist increased adiponectin release only from the brown adipocytes isolated from lean Zucker rats. It is the conclusive difference between obese (fa/fa) Zucker rats and lean Zucker rats that plasma adiponectin levels of obese (fa/fa) Zucker rats are significantly higher than those of lean Zucker rats. Moreover, we clarified that mRNA expression level of adiponectin receptor 1 in RT WAT, BAT, and liver of obese (fa/fa) Zucker rats is low despite high plasma adiponectin level, and low expression of PPARs in BAT leads to less sensibility of adiponectin release from brown adipocytes to a PPAR gamma agonist in obese (fa/fa) Zucker rats.     

Effect of hexachlorobenzene on NADPH-generating lipogenic enzymes and L-glycerol-3-phosphate dehydrogenase in brown adipose tissue.

The effect of the in vivo administration of hexachlorobenzene (HCB) (100 mg/100 g bw) for 30 days, on the activities of brown adipose tissue (BAT) lipogenic enzymes, i.e. malic enzyme (ME), and glucose-6-phosphate dehydrogenase (G6PD) and the mitochondrial non lipogenic enzyme, L-glycerol-3-phosphate dehydrogenase (LG3PD), was studied in male Wistar rats, submitted to various neurohormonal manipulations. BAT ME, G6PD and LG3PD activities showed significant reductions in response to HCB treatment both in euthyroid and surgically thyroidectomized rats, showing that the effect does not depend on the presence of thyroid hormones. These results differ from those obtained for hepatic ME and G6PD activities, which increased in HCB intoxicated rats without alteration in LG3PD. HCB decreased BAT ME activity under BAT denervation. Administration of HCB resulted in time and dose-dependent decreases in the activity of BAT malic enzyme. The basal activity of ME was increased in hypothyroid rats, while that of LG3PD was reduced. A stimulatory effect of receptor-saturating doses of triiodothyronine (T3) (50 microg/100 g body weight) was observed on BAT ME and LG3PD activities in thyroidectomized rats, showing that the enzymes responded to thyroid hormone stimulation in a normal manner. The stimulatory effect of saturating doses of T3 on ME and LG3PD was reduced by HCB. The results presented herein unequivocally show that brown adipose tissue is a specific target in HCB-induced toxicity, which in turn involves severe alterations in the regulation of BAT lipogenesis.     

The effects of 2-deoxy-D-glucose on brown adipose tissue of lean and obese Zucker rats

The response of brown adipose tissue (BAT) thermogenesis, as measured by mitochondrial GDP binding, of lean and obese Zucker fa/fa rats to 2-deoxy-D-glucose (2-DOG) has been investigated. 2-DOG reduced BAT mitochondrial GDP binding of lean rats but had no effect in obese rats. Adrenalectomy increased BAT GDP binding in obese rats and restored the 2-DOG inhibitory effect. Corticosterone inhibited GDP binding in lean rats and abolished the 2-DOG inhibitory effect. 2-DOG induced hyperphagia and hyperglycaemia in lean rats, but these effects were either absent or attenuated in the obese. The possibility that a glucocorticoid inhibition of glucose metabolism impairs sympathetic activity in the obese rats is discussed.     

Low temperature stimulates pineal activity in Syrian hamsters

The effect of 24-hr exposure to cold (5 degrees C) was studied in male Syrian hamsters adapted to short days (LD 8:16). Both pineal N-acetyltransferase (NAT) activity and pineal and serum concentrations of melatonin showed a clear, diel rhythm with a moderate but significant increase late in the dark period. The nighttime peak levels of NAT activity and pineal and serum melatonin were significantly higher in the animals that had been exposed to cold than in those remaining in warm (22 degrees C) conditions. The activity of type-II 5'-deiodinase (5'D) in the brown adipose tissue (BAT) was not different after 24 hr of cold exposure between cold- and warm-exposed hamsters, and the enzyme did not show any diel rhythmicity. It has been speculated that some effects of cold exposure may be simulated by melatonin treatment; the present data further support this notion. The apparent lack of response in BAT 5'D activity remains enigmatic and needs further investigation.