Hypertrophy Of Brown Adipose Tissue Research Articles

Increased Aquaporin-7 Expression Is Associated with Changes in Rat Brown Adipose Tissue Whitening in Obesity: Impact of Cold Exposure and Bariatric Surgery

Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in adipocytes, in the improvement of brown adipose tissue (BAT) whitening, a process whereby brown adipocytes differentiate into white-like unilocular cells, after cold exposure or bariatric surgery in male Wistar rats with diet-induced obesity (DIO) (n = 229). DIO promoted BAT whitening, evidenced by increased BAT hypertrophy, steatosis and upregulation of the lipogenic factors Pparg2, Mogat2 and Dgat1. AQP7 was detected in BAT capillary endothelial cells and brown adipocytes, and its expression was upregulated by DIO. Interestingly, AQP7 gene and protein expressions were downregulated after cold exposure (4 °C) for 1 week or one month after sleeve gastrectomy in parallel to the improvement of BAT whitening. Moreover, Aqp7 mRNA expression was positively associated with transcripts of the lipogenic factors Pparg2, Mogat2 and Dgat1 and regulated by lipogenic (ghrelin) and lipolytic (isoproterenol and leptin) signals. Together, the upregulation of AQP7 in DIO might contribute to glycerol influx used for triacylglycerol synthesis in brown adipocytes, and hence, BAT whitening. This process is reversible by cold exposure and bariatric surgery, thereby suggesting the potential of targeting BAT AQP7 as an anti-obesity therapy.

Disease progression promotes changes in adipose tissue signatures in type 2 diabetic (db/db) mice: The potential pathophysiological role of batokines

Unlike the white adipose tissue (WAT) which mainly stores excess energy as fat, brown adipose tissue (BAT) has become physiologically important and therapeutically relevant for its prominent role in regulating energy metabolism. The current study makes use of an established animal model of type 2 diabetes (T2D) db/db mice to determine the effect of the disease progression on adipose tissue morphology and gene regulatory signatures. Results showed that WAT and BAT from db/db mice display a hypertrophied phenotype that is consistent with increased expression of the pro-inflammatory cytokine, tumor necrosis factor-alpha (Tnf-α). Moreover, BAT from both db/db and non-diabetic db/+ control mice displayed an age-related impairment in glucose homeostasis, inflammatory profile, and thermogenic regulation, as demonstrated by reduced expression of genes like glucose transporter (Glut-4), adiponectin (AdipoQ), and uncoupling protein 1 (Ucp-1). Importantly, gene expression of the batokines regulating sympathetic neurite outgrowth and vascularization, including bone morphogenic protein 8b (Bmp8b), fibroblast growth factor 21 (Fgf-21), neuregulin 4 (Nrg-4) were altered in BAT from db/db mice. Likewise, gene expression of meteorin-like (Metrnl), growth differentiation factor 15 (Gdt-15), and C-X-C motif chemokine-14 (Cxcl-14) regulating pro- and anti-inflammation were altered. This data provides some new insights into the pathophysiological mechanisms involved in BAT hypertrophy (or whitening) and the disturbances of batokines during the development and progression of T2D. However, these are only preliminary results as additional experiments are necessary to confirm these findings in other experimental models of T2D.

Sympathetic innervation suppresses the autophagic-lysosomal system in brown adipose tissue under basal and cold-stimulated conditions.

The sympathetic nervous system (SNS) activates cAMP signaling and promotes trophic effects on brown adipose tissue (BAT) through poorly understood mechanisms. Because norepinephrine has been found to induce antiproteolytic effects on muscle and heart, we hypothesized that the SNS could inhibit autophagy in interscapular BAT (IBAT). Here, we describe that selective sympathetic denervation of rat IBAT kept at 25°C induced atrophy, and in parallel dephosphorylated forkhead box class O (FoxO), and increased cathepsin activity, autophagic flux, autophagosome formation, and expression of autophagy-related genes. Conversely, cold stimulus (4°C) for up to 72 h induced thermogenesis and IBAT hypertrophy, an anabolic effect that was associated with inhibition of cathepsin activity, autophagic flux, and autophagosome formation. These effects were abrogated by sympathetic denervation, which also upregulated Gabarapl1 mRNA. In addition, the cold-driven sympathetic activation stimulated the mechanistic target of rapamycin (mTOR) pathway, leading to the enhancement of protein synthesis, evaluated in vivo by puromycin incorporation, and to the inhibitory phosphorylation of Unc51-like kinase-1, a key protein in the initiation of autophagy. This coincided with a higher content of exchange protein-1 directly activated by cAMP (Epac1), a cAMP effector, and phosphorylation of Akt at Thr308, all these effects being abolished by denervation. Systemic treatment with norepinephrine for 72 h mimicked most of the cold effects on IBAT. These data suggest that the noradrenergic sympathetic inputs to IBAT restrain basal autophagy via suppression of FoxO and, in the setting of cold, stimulate protein synthesis via the Epac/Akt/mTOR-dependent pathway and suppress the autophagosome formation, probably through posttranscriptional mechanisms.NEW & NOTEWORTHY The underlying mechanisms related to the anabolic role of sympathetic innervation on brown adipose tissue (BAT) are unclear. We show that sympathetic denervation activates autophagic-lysosomal degradation, leading to a loss of mitochondrial proteins and BAT atrophy. Conversely, cold-driven sympathetic activation suppresses autophagy and stimulates protein synthesis, leading to BAT hypertrophy. Given its high-potential capacity for heat production, understanding the mechanisms that contribute to BAT mass is important to optimize chances of survival for endotherms in cold ambients.

Energy dissipation in brown adipose tissue: From mice to men

In rodents, brown adipose tissue (BAT) is a metabolic organ that produces heat in response to cold and dietary intake through mitochondrial uncoupling. For long time, BAT was considered to be solely important in small mammals and infants, however recent studies have shown that BAT is also functional in adult humans. Interestingly, the presence and/or functionality of this thermogenic tissue is diminished in obese people, suggesting a link between human BAT and body weight regulation. In the last years, evidence has also emerged for the existence of adipocytes that may have an intermediate thermogenic phenotype between white and brown adipocytes, so called brite or beige adipocytes. Together, these findings have resulted in a renewed interested in (human) brown adipose tissue and pathways to increase the activity and recruitment of these thermogenic cells. Stimulating BAT hypertrophy and hyperplasia in humans could be a potential strategy to target obesity. Here we will review suggested pathways leading to BAT activation in humans, and discuss novel putative BAT activators in rodents into human perspective.

DoubleMyodandIgf2inactivation promotes brown adipose tissue development by increasingPrdm16expression

Brown fat or brown adipose tissue (BAT), found in newborn mammals as small depots localized in the interscapular region, plays a prominent role in regulating thermogenesis perinatally. The physiological importance of functional BAT has been recently reasserted in human adults. Because myoblasts and adipoblasts emerge from a common mesodermal precursor, we investigated developmental determination and the reciprocal relationship between muscle and adipocyte commitment. Here we show that a mutant mouse defective for both Igf2 and Myod genes exhibits massive BAT hypertrophy compared with wild-type and single-mutant newborns. The increased adipocyte proliferation in BAT of double-mutant newborns was associated with overexpression of the brown fat-specific marker Ucp1. More strikingly, expression of the master key gene Prdm16 involved in the switch between myogenic and brown adipogenic lineages was drastically enhanced. We further demonstrate that concomitant Myod and Igf2 inactivation accelerates differentiation of a brown preadipocyte cell line and induces lipid accumulation and increased Ucp1 and Prdm16 expression. This in vitro approach brings additional support for the implication of both Myod and Igf2 in BAT development. These results provide the first in vivo evidence that a myogenic regulator together with a growth factor act simultaneously but through independent pathways to repress Prdm16, which opens potential therapeutic perspectives for human metabolic disorders.

Brown fat thermogenesis in cold-acclimated rats is not abolished by the suppression of thyroid function.

The effects of long-term cold exposure on brown adipose tissue (BAT) thermogenesis in hypothyroid rats have been examined. Thyroid ablation was performed in normal rats after 2 mo of exposure to 4 degrees C, when BAT hypertrophy and thermogenic activity were maximal. After ablation, hypothyroid and normal controls remained in the cold for 2 additional months. At the end of the 4-mo cold exposure, all untreated hypothyroid rats were alive, had normal body temperature, and had gained an average 12.8% more weight than normal controls. Long-term cold exposure of hypothyroid rats markedly increased BAT weight, mitochondrial proteins, uncoupling protein (UCP)-1, mRNA for UCP-1, and oxygen consumption to levels similar to those seen in cold-exposed normal rats. The results indicate that thyroid hormones are required for increased thermogenic capacity to occur as an adaptation to long-term cold exposure. However, cold adaptation can be maintained in the absence of thyroid hormone.

Changes of adiposity in response to vitamin A status correlate with changes of PPAR gamma 2 expression.

To gain insight into the in vivo modulation of the expression of the adipogenic transcription factors PPAR gamma 2, C/EBP alpha, and ADD1/SREBP1c by retinoids and its relationship with whole-body adiposity. Three-week-old mice were fed with standard chow or a vitamin A-deficient diet for 10 weeks. During the 4 days immediately before they were killed, the animals were treated either with all-trans retinoic acid (tRA; 100 mg/kg per day, subcutaneously) or vehicle. The specific levels of the mRNAs for the three transcription factors were analyzed in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue and in brown adipose tissue (BAT). Other parameters determined were leptin and UCP2 levels in white adipose tissue depots, total cholesterol and triglyceride serum levels, energy intake, body weight, and adiposity. Vitamin A-deficient diet feeding led to a marked increase of adiposity and to a small increase of body weight. Hypertrophy of white adipose tissue depots correlated with enhanced PPAR gamma 2 expression. Hypertrophy of BAT, in contrast, correlated with a decrease of PPAR gamma 2 expression that may contribute to the known reduced thermogenic potential of BAT under conditions of vitamin A restriction. Treatment with tRA triggered a reduction of adiposity and body weight that correlated with a down-regulation of PPAR gamma 2 expression in all adipose tissues. The effects of tRA were more pronounced in eWAT, where C/EBP alpha and ADD1/SREBP1c levels were also reduced. The response to tRA was impaired in the eWAT and BAT of animals fed the vitamin A-deficient diet. The results emphasize the importance of retinoids as physiological regulators of adipose tissue development and function in intact animals.

Sympathoadrenal hyperactivity and the etiology of neuroleptic malignant syndrome.

The author's goal was to develop a pathophysiological model for neuroleptic malignant syndrome with greater explanatory power than the alternative hypotheses of hypothalamic dopamine antagonism (elevated set point) and direct myotoxicity (malignant hyperthermia variant). Published clinical findings on neuroleptic malignant syndrome were integrated with data from human and animal studies of muscle physiology, thermoregulation, and autonomic nervous system function. The data show that the sympathetic nervous system's latent capacity for autonomous activity is expressed when tonic inhibitory inputs from higher central nervous system centers are disrupted. These tonic inhibitory inputs are relayed to preganglionic sympathetic neurons by way of dopaminergic hypothalamospinal tracts. The sympathetic nervous system mediates hypothalamic coordination of thermoregulatory activity and is a primary regulator of muscle tone and thermogenesis, augmenting both of these when stimulated. In addition, the sympathetic nervous system modulates all of the other end-organs that function abnormally in neuroleptic malignant syndrome. There is substantial evidence to support the hypothesis that dysregulated sympathetic nervous system hyperactivity is responsible for most, if not all, features of neuroleptic malignant syndrome. A predisposition to more extreme sympathetic nervous system activation and/or dysfunction in response to emotional or psychological stress may constitute a trait vulnerability for neuroleptic malignant syndrome, which, when coupled with state variables such as acute psychic distress or dopamine receptor antagonism, produces the clinical syndrome of neuroleptic malignant syndrome. This hypothesis provides a more comprehensive explanation for existing clinical data than do the current alternatives.

Desensitization of the beta-adrenergic response in human brown adipocytes.

Activation of adenylyl cyclase by beta-adrenergic receptors (betaARs) plays a major role in adipose tissue homeostasis. The increase in cAMP promotes lipolysis in white adipose tissue, activates both thermogenesis and lipolysis in brown adipose tissue (BAT), and induces BAT hypertrophy. Previous studies indicated that among the three betaAR subtypes present in adipose tissue, beta3AR could be a potential target for antiobesity treatments in humans. We studied immortalized human brown adipocytes (PAZ6 adipocytes) as a model of beta-adrenergic response in human BAT. PAZ6 adipocytes and freshly isolated mature human brown adipocytes display the same proportions of betaAR subtypes, with beta3AR being the most abundant (approximately 80% of the total). However, beta3AR was poorly coupled to the adenylyl cyclase pathway in PAZ6 cells, contributing to only 10% of the isoproterenol-induced accumulation of cAMP, whereas 20% and 70% of the signal depended on beta1- and beta2-subtypes, respectively. Upon isoproterenol stimulation, beta1- and beta2AR down-regulated with a half-life of about 3 h and the beta3AR with a half-life of 30-40 h. Long term stimulation with both saturating (micromolar) and nonsaturating (nanomolar) concentrations of beta-adrenergic agonists caused a complete desensitization of the beta-adrenergic response at the adenylyl cyclase level and loss of stimulated protein kinase A activity and CREB phosphorylation. These results suggest that cAMP-dependent processes will be desensitized upon permanent treatment with beta3AR agonists. Further studies should establish whether the beta3AR is coupled to other signaling pathways in human brown adipocytes and whether these may contribute to BAT hypertrophy and/or thermogenesis.

Growth Performance of Rats Fed Jojoba Proteins. Possible Correlations with Trypsin Inhibitory Activity in Jojoba Proteins

The effects of the water-soluble protein fraction of jojoba meal on growth and relative organ weight in rats were tested. Trypsin inhibitory activity (TIA) was measured in the untreated water-soluble jojoba proteins and in preparations after dry-heating (100 °C, 2 h) or methanol extraction (Soxhlet, 6 h). TIA was found in the jojoba protein fraction and could not be destroyed by dry-heating or methanol extraction of the jojoba proteins. In the first feeding experiment, growth performance and relative organ weight were compared of young rats fed ad libitum a diet containing either 18% soybean proteins (C), 6% soybean proteins (P6), or 6% soybean proteins supplemented with 12% jojoba proteins (JJ) or 12% toasted jojoba proteins (JJT). In a second 3 week experiment, growth and relative organ weight of young rats receiving a diet containing 6% soybean proteins supplemented with 12% methanol-extracted jojoba proteins (JJM) were compared for rats pair-fed with JJM with a diet containing 18% soybean proteins (PF). Although food intakes of C, JJ, and JJT rats were similar and P6 rats ate more than C rats, P6, JJ, and JJT rats showed growth retardation compared to C rats. JJM rats and PF rats showed a similar growth. The pancreas was hypertrophied in JJ and JJT rats, compared to C rats, and in JJM rats, compared to PF rats. Interscapular brown adipose tissue (BAT) was hypertrophied in P6, JJ, and JJT rats but normal in the JJM group. Jojoba proteins induce growth retardation. This is accompanied by pancreatic and BAT hypertrophy. As trypsin inhibition does not change but growth does ameliorate and BAT hypertrophy is abolished after methanol extraction, trypsin inhibition has no major influence on growth in the present experiments, while BAT hypertrophy is accompanied by growth reduction. Keywords: Simmondsia chinensis; jojoba meal; jojoba protein concentrate; rat

Appearance of brown adipocytes in white adipose tissue during CL 316,243-induced reversal of obesity and diabetes in Zucker fa/fa rats.

In our previous studies, chronic treatment of rats with a new beta 3-adrenoceptor agonist, CL 316,243, retarded diet-induced obesity and promoted thermogenesis in young animals and reversed established diet-induced obesity in older animals that continued to eat a high fat diet. Reversal of obesity was associated with shrinking of enlarged white adipocytes but the number of mature white adipocytes, which had not been increased by the diet, was not reduced. Drug-treatment induced appearance of abundant brown adipocytes in white adipose tissue (WAT) depots as well as hypertrophy of brown adipose tissue (BAT) in both lean and diet-induced obese rats. To find out whether the known hyperplasia of white adipocytes in the obese fa/fa rat could be reversed by CL 316,243-treatment and whether the grossly enlarged WAT depots of the obese fa/fa rat contain precursors to brown adipocytes. CL 316,243 infusion (1 mg/kg/d) reduced abdominal fat. The loss of fat was due to a decrease in white adipocyte size, with no loss of the markedly elevated number of adipocytes in the fa/fa rats. Resting metabolic rate increased by 40% in lean rats, by 70% in fa/fa rats. Food intake decreased in the hyperphagic fa/fa rats but did not change in lean rats, in both lean and fa/fa rats, a marked increase in protein content of retroperitoneal WAT was associated with appearance of abundant densely-stained brown adipocytes expressing uncoupling protein (UCP) but total number of cells (from DNA content) actually decreased. Hyperinsulinemia and hyperglycemia of fa/fa rats were reduced by treatment, indicating improved sensitivity to insulin. Abundant precursors to brown adipocytes are present in WAT depots of fa/fa rats and much of the exaggerated increase in resting metabolic rate induced by CL 316,243 occurs in these cells. This beta 3-adrenoceptor agonist is an effective anti-obesity and anti-diabetic agent in fa/fa rats. It does not bring about disappearance of mature white adipocytes but does bring about a remodelling of WAT, with a marked change in cell composition.

Stimulation of brown adipose tissue activity in tumor-bearing rats.

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.

Meal associated changes in brown fat thermogenesis and glycogen

Data indicate a close association between a decrease in feeding-induced brown adipose tissue (BAT) thermogenesis and an increase in food consumption. The present study examines the hypothesis that feeding-induced BAT thermogenesis, or feeding-induced changes in BAT glycogen, a mobile form of energy store and a correlate of BAT thermogenesis, may modulate feeding behavior. We report that propranolol, which completely abolished meal-induced BAT thermogenesis, did not evoke intake of a larger meal. Though BAT glycogen concentration is a sensitive measure of the state of feeding, on a meal to meal basis it does not correlate with hunger and satiety. Hence the hypothesis is not supported by the current data. We also report that meal-induced BAT hypertrophy and glycogen deposition can be dissociated from meal-induced BAT thermogenesis.

Effects of short photoperiod and melatonin treatment on thermogenesis in the Syrian hamster.

This study investigated whether short photoperiod or melatonin-treatment could alter the thermogenic capacity of Syrian hamsters. Exposure of hamsters to short photoperiod and to exogenous melatonin treatment induced gonadal regression and hypertrophy of brown adipose tissue (BAT). Short photoperiod and melatonin-induced BAT hypertrophy was not accompanied by any change in noradrenaline (NA) turnover in this tissue. The concentration of NA was significantly decreased in hypertrophied BAT, indicating that sympathetic innervation in BAT did not effect its hypertrophy. No improvement in nonshivering thermogenic capacity was noticed in hamsters with increased BAT mass. However, capability for shivering thermogenesis seemed to be enhanced in melatonin-treated hamsters. These observations suggest that melatonin, in addition to mediating short photoperiod-induced gonadal regression in the Syrian hamster, also brings about thermoregulatory adjustments necessary for hibernation.

Thyroxine 5'-deiodinase in brown adipose tissue of myopathic hamsters.

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.

Brown Adipose Tissue Thermogenesis during Pregnancy in Mice

The thermogenic activity of interscapular brown adipose tissue has been assessed at different stages of pregnancy in mice. In late pregnancy there was a hypertrophy of the tissue which reversed at parturition. Neither the total protein content nor the total cytochrome oxidase activity of the tissue changed significantly throughout pregnancy or into early lactation (2-3 days, post-partum). However, mitochondrial GDP binding, an index of the activity of the proton conductance pathway, was significantly decreased at the end of pregnancy with a further decrease in early lactation. Moderate food restriction had no effect on either cytochrome oxidase activity or mitochondrial GDP binding at the end of pregnancy, as compared with pregnant animals fed ad libitum. Food restriction did, however, prevent the hypertrophy of brown adipose tissue in late pregnancy. It is concluded that brown adipose tissue thermogenesis is not significantly decreased in the pregnant mouse until shortly before parturition, even in animals subject to food restriction. It is also concluded that the normal dietary stimulation of thermogenesis in response to hyperphagia is suppressed in the pregnant animal.

Defective thermoregulatory thermogenesis in monosodium glutamate-induced obesity in mice

We have studied thermoregulatory thermogenesis in mice rendered obese by neonatal administration of monosodium glutamate (MSG) and in saline treated controls. At 12 weeks of age MSG-treated mice maintained on a chow diet and housed at 24 °C, exhibited hypertrophy of brown adipose tissue (BAT) compared to controls (65% increase in wet weight and lipid content, no difference in DNA content). Acute cold exposure (4 °C for two hours) resulted in a significantly greater fall in core temperature in MSG-treated than control mice. After cold exposure to 4 °C for six hours, control animals mobilized BAT lipid whereas MSG-treated animals did not. Both groups showed comparable increments in oxygen consumption in response to exogenous norepinephrine. The above changes were qualitatively the same for both male and female animals. The following conclusions were reached: (1) MSG-treated mice have defective cold induced thermogenesis, indirect evidence suggests this results from impaired activation of thermogenic mechanisms in BAT; (2) the defect responsible for this lies extrinsic to BAT; and (3) the quantitative significance of defective thermoregulatory thermogenesis for the development of obesity in these mice is uncertain.

Brown adipose tissue is a major site of glucose utilisation in [formula omitted] mice treated with a thermogenic β-adrenoceptor agonist

Chronic treatment of C57B1 6 ob ob mice with the thermogenic β-adrenoceptor agonist BRL 26830 increased the maximal activities of hexokinase and phosphofructokinase 2- and 3-fold respectively in interscapular brown adipose tissue. Combining measurements of whole body glucose turnover with measurements of the uptake of 2-deoxyglucose by tissues in vivo has allowed tissue rates of glucose utilisation to be calculated. Under basal conditions, brown adipose tissue accounts for only 1.6% of the whole body rate of glucose utilisation. This is increased to 3.7% in mice given a single dose of BRL 26830. In ob ob mice treated chronically with BRL 26830, which causes brown adipose tissue hypertrophy, glucose utilisation by this tissue was increased to 4.1% of the whole body rate under the basal condition. In these mice, an additional acute treatment with BRL 26830 increased brown adipose tissue glucose utilisation rate to 12.5% of the whole body rate.

Defective trophic response of brown adipose tissue of myopathic hamsters.

Hamsters with muscular dystrophy (BIO 14.6) have a smaller than normal amount of brown adipose tissue. Two stimuli that promote growth of brown adipose tissue in normal hamsters, short photoperiod and eating a high-fat diet, are here shown to be without effect on brown adipose tissue of myopathic hamsters. Cold-induced growth of brown adipose tissue occurs normally [Am. J. Physiol. 239 (Cell Physiol. 8): C18-C22, 1980]. There is a normal rate of turnover of norepinephrine in brown adipose tissue of the myopathic hamster but a failure of the tissue to hypertrophy in response to norepinephrine is unlikely since norepinephrine does not appear to mediate the trophic response [Am. J. Physiol. 247 (Endocrinol. Metab. 10): E793-E799, 1984]. Denervation results in a marked reduction in size (protein content) of brown adipose tissue of normal hamsters but has very little effect on the size of brown adipose tissue of myopathic hamsters. A central, possibly hypothalamic, defect in the myopathic hamster is postulated to underlie its abnormal control of brown adipose tissue hypertrophy.

Brown adipose tissue and thermogenesis in hypophysectomized rats in relation to temperature acclimation

The aim of this work was to test the role of pituitary dependent hormones in cold-induced non-shivering thermogenesis. In the 28 degrees C-acclimated rat, hypophysectomy inhibited body growth and led to an atrophy of thyroid and adrenals. In brown adipose tissue (BAT) some alterations were induced which are usually observed after cold acclimation of the animal: increase in relative weight, decreases in the relative amount of lipids, increases in the amounts of protein and DNA and modification of the proportions of several phospholipid fatty acids; moreover, basal lipolysis, in vitro, was enhanced to the same extent as that following cold acclimation of the normal rat. The in vivo stimulation by norepinephrine (NE) of O2 consumption (test for nonshivering thermogenesis) and of fatty acid release into blood were suppressed. Progressive cold acclimation of the hypophysectomized rats at 15 degrees C led to a hypertrophy of BAT to the same extent as in the sham-operated animals. The in vivo sensitivity to NE was partially restored. The results suggest that hypophysectomy does not suppress the ability to acclimate to moderate cold by means of BAT dependent non-shivering thermogenesis. However, the low ability to produce heat seems to indicate that pituitary or pituitary-dependent hormones are necessary to optimize the cold stimulation of brown fat thermogenesis.