Brown Adipose Tissue Thermogenic Activity Research Articles

Brown-fat paucity due to impaired BMP signalling induces compensatory browning of white fat

SummaryMaintenance of body temperature is essential for survival of homeotherms. Brown adipose tissue (BAT) is a specialized fat tissue that is dedicated to thermoregulation1. Due to its remarkable capacity to dissipate stored energy and its demonstrated presence in adult humans2-5, BAT holds great promise for the treatment of obesity and metabolic syndrome1. Rodent data suggest the existence of two types of brown fat cells: the constitutive BAT (cBAT), which is of embryonic origin and anatomically located in the interscapular region of mice, and the recruitable BAT (rBAT) that resides within white adipose tissue (WAT)6 and skeletal muscle7, that has alternatively been called beige8, brite9, or inducible BAT10. Bone morphogenetic proteins (BMPs) regulate the formation and thermogenic activity of BAT10-12. We here provide evidence for a systemically active regulatory mechanism that serves to control whole body BAT-activity for thermoregulation and energy homeostasis. Genetic ablation of type 1A BMP-receptor (Bmpr1A) in brown adipogenic progenitor cells leads to a severe paucity of cBAT. This in turn increases sympathetic input to WAT, thereby promoting the formation of rBAT within white fat depots. This previously unknown compensatory mechanism, aimed at restoring total brown fat-mediated thermogenic capacity in the body, is sufficient to maintain normal temperature homeostasis and resistance to diet-induced obesity. These data suggest an important physiological cross-talk between the constitutive and recruitable brown fat cells. This sophisticated regulatory mechanism of body temperature may participate in the control of energy balance and metabolic disease.

Brun, blanc, beige : la couleur du gras et nouvelles perspectives thérapeutiques de l’obésité…

Three articles published in the NEJM in 2009 have renewed the interest for brown adipose tissue (BAT) in humans. This review reports interesting new findings on adipocyte cell types that have been presented at the last meeting of the Endocrine Society in Houston, TX, in June 2012. Many studies have focused on identifying factors involved in brown adipocyte lineage, the site of adaptive thermogenesis. Indeed, the role of the transcription factors, such as PRDM16, in brown adipocyte differentiation has been unambiguously established. Very recently, the concept of “beigeing”, defined as the occurence of thermogenic brown adipocytes in white adipose tissue, has emerged, leading to the identification, by Bruce Spiegelman's group, of a new muscular hormone, called irisin, which is able to stimulate the “beigeing”. This finding should convey toward the discovery of new mutations involved in the pathogenesis of obesity and lipodystrophies, and should be translated into innovative therapeutic perspectives. Finally, the nature of BAT innervation has been clarified and the presence of an autoregulatory loop between BAT and notably hypothalamic paraventricular nuclei via the sensory and sympathetic nervous systems has been delineated. These feedback circuits appear to be crucial to control BAT thermogenic activity.

Peroxisome Proliferator-activated Receptor-γ Coactivator-1α Controls Transcription of the Sirt3 Gene, an Essential Component of the Thermogenic Brown Adipocyte Phenotype

Sirt3 (silent mating type information regulation 2, homolog 3), a member of the sirtuin family of protein deacetylases with multiple actions on metabolism and gene expression is expressed in association with brown adipocyte differentiation. Using Sirt3-null brown adipocytes, we determined that Sirt3 is required for an appropriate responsiveness of cells to noradrenergic, cAMP-mediated activation of the expression of brown adipose tissue thermogenic genes. The transcriptional coactivator Pgc-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) induced Sirt3 gene expression in white adipocytes and embryonic fibroblasts as part of its overall induction of a brown adipose tissue-specific pattern of gene expression. In cells lacking Sirt3, Pgc-1α failed to fully induce the expression of brown fat-specific thermogenic genes. Pgc-1α activates Sirt3 gene transcription through coactivation of the orphan nuclear receptor Err (estrogen-related receptor)-α, which bound the proximal Sirt3 gene promoter region. Errα knockdown assays indicated that Errα is required for full induction of Sirt3 gene expression in response to Pgc-1α. The present results indicate that Pgc-1α controls Sirt3 gene expression and this action is an essential component of the overall mechanisms by which Pgc-1α induces the full acquisition of a brown adipocyte differentiated phenotype.

Stress-Induced Hypertension and Increased Sympathetic Activity in Mice Overexpressing Neuropeptide Y in Noradrenergic Neurons

Background and Aims: Neuropeptide Y (NPY) is a sympathetic neurotransmitter co-stored and co-released with noradrenaline and adrenaline. We have constructed a novel NPY transgenic mouse model (OE-NPY^DBH mouse) where targeted overexpression results in increased levels of NPY in the brainstem and adrenal glands. The present study was aimed to understand the role of NPY released from sympathetic nerves and brain noradrenergic neurons in regulation of blood pressure, and behavioral responses to stress. Methods: Blood pressure was measured by radiotelemetry in conscious male OE-NPY^DBH and wild-type mice during surgical stress and in baseline conditions. Plasma and adrenal gland catecholamine levels were measured at baseline. Acute immobilization and cold exposure were used to study the plasma levels of NPY and corticosterone in stress, and brown adipose tissue thermogenic activity was measured with [³H]GDP binding after cold. Results: Here, we demonstrate that sympathoadrenal activity is enhanced in the OE-NPY^DBH mice. Blood pressure during surgical stress was significantly increased in comparison with wild-type controls. Furthermore, OE-NPY^DBH mice showed sexually dimorphic NPY responses to stress, and an anxiolytic-like behavior in elevated plus-maze and light-dark tests. Conclusion: This study shows that the overactive noradrenergic NPY system plays a role in regulation of blood pressure and adaptive responses to stress, and may be a link between chronic stress and adiposity-associated disturbances in metabolism.

Sex Differences in Brown Adipose Tissue Thermogenic Features During Caloric Restriction

Caloric restriction (CR) studies have shown that females rats conserve energy more efficiently, showing a higher resistance to weight loss and higher protection of vital organs mass than male rats. Gender-dependent inactivation of thermogenesis in brown adipose tissue (BAT) has been proposed as one of these possible energy conserving mechanisms. To study the changes underlying this inactivation in rats, a three month study with 40% CR was undertaken to unravel the effects on BAT recruitment. Under ad libitum conditions female rats had greater BAT recruitment and greater oxygen consumption than their male counterparts. Total and mitochondrial protein, as well as triglyceride and DNA content were more reduced in restricted female rats than in restricted males. Similarly, the levels of key BAT functional proteins (UCP1, LPL, HSL, TFAM) were more reduced in restricted females, whereas no changes were found in mitochondrial DNA levels (mtDNA) and OXPHOS activities in males and females. Furthermore, α _2A/β ₃ adrenergic receptor ratio remained constant in male rats whereas in female rats CR increased 60%. In conclusion, our results suggest that female rats, whose BAT thermogenic activity is higher in ad libitum conditions, is depressed during CR. This inactivation involves the mitochondrial differentiation process and lipolytic system and could be due, at least in part, to the unfavourable adrenergic receptor balance for thermogenic activation.

CIDE-A, a novel link between brown adipose tissue and obesity

Brown adipose tissue (BAT) is the major site of adaptive thermogenesis in rodents. The thermogenic activity of BAT is mediated by uncoupling proteins (Ucp1). Impaired BAT activity is believed to have an important role in the development of obesity. However, direct evidence linking BAT to obesity is scarce. Cidea, which was initially identified as a result of its sequence similarity to the apoptotic DNA fragmentation factor, is highly expressed in BAT. Mice that are deficient for Cidea showed an increase in energy expenditure and are resistant to high-fat diet-induced obesity and diabetes. Although the precise mechanism by which Cidea regulates energy homeostasis is not yet clear, Cidea appears to interact with Ucp1 in mammalian cells and inhibits its uncoupling activity when co-expressed in yeast. Therefore, Cidea offers a new option to explore the linkage between BAT and obesity.

Obesity in transgenic female mice with constitutively elevated luteinizing hormone secretion.

Transgenic (TG) female mice, expressing a chimeric bovine luteinizing hormone (LH) beta-subunit/human chorionic gonadotropin beta-subunit COOH-terminal extension (bLHbeta-CTP) gene, produce high levels of circulating LH and serve as a model for functional ovarian hyperandrogenism and follicular cysts. We report here that obesity is a typical feature of these female mice. The mean body weight of the bLHbeta-CTP females was significantly higher than in controls at, and beyond 5 wk of age, and at 5 mo, it was 32% increased. At this age, the amount of white adipose tissue in the bLHbeta-CTP females was significantly increased, as reflected by the weight difference of the retroperitoneal fat pad. In addition, the expression of leptin mRNA in white adipose tissue of the TG females was elevated about twofold. Serum leptin and insulin levels, and food intake, were also increased significantly in the TG females. Brown adipose tissue (BAT) thermogenic activity, as measured by GDP binding to BAT mitochondria, was reduced (P < 0.05). Ovariectomy at the age of 3 wk totally prevented the development of obesity. In summary, the present results show that intact female bLHbeta-CTP mice are obese, have increased food consumption, and reduced BAT thermogenic activity. The weight gain can be explained partly by elevated androgens but is probably also contributed to the increased adrenal steroidogenesis. Hence, the bLHbeta-CTP mice provide a useful model for studying obesity related to elevated LH secretion, with consequent alterations in ovarian and adrenal function.

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.

Effect of date of mating and housing on lamb growth, adipose tissue deposition and plasma leptin concentrations

In lambs, the rapid increase in heat production after birth is due to initiation of nonshivering thermogenesis in brown adipose tissue (BAT). This occurs in conjunction with an increase in amount and activity of BAT specific uncoupling protein 1 (UCP1) (Clarke et al. 1997). UCP1 abundance and activity is low in fetal life but, within twelve hours of birth, there is an increase in the thermogenic activity of BAT and mRNA for UCP1. This ontogeny of UCP1 mRNA in BAT is very similar that of leptin, which is first detectable in the sheep fetus at 90 days gestation in fetal adipose tissue, its expression then increases up to term at 147 days (Yuen et al 1999). Leptin is a hormone which is thought to play a physiological role is in energy balance, it is primarily produced by white adipose tissue although there is evidence for its production in both brown adipose tissue and the placenta. Lambs born in the autumn are known to be smaller than those born in the spring (McCoard et al. 1997). It is not known if moderate changes in date of mating can influence birth weight or adipose tissue development. The present study aimed to determine whether date of mating could influence lamb birth weight, the abundance of BAT, UCP1, plasma leptin.

Thermogenesis and fatty acid composition of brown adipose tissue in rats rendered hyperthyroid and hypothyroid-with special reference to docosahexaenoic acid.

The effects of hyperthyroidism and hypothyroidism on brown adipose tissue (BAT) thermogenesis and phospholipid fatty acid composition were investigated in rats. Chronic triiodothyronine (T3) treatment (hyperthyroidism) increased the interscapular BAT pad weight, its triacylglycerol content, and its DNA content. It did not affect basal and noradrenaline-stimulated in vitro oxygen consumption of BAT expressed per microg DNA, although it significantly increased the oxygen consumption of the whole BAT pad. T3 treatment had little effect on phospholipid content and phospholipid fatty acid composition. In contrast, chronic methimazole treatment (hypothyroidism) decreased the BAT pad weight and the triacylglycerol content, but did not significantly change the DNA content in comparison with the control. It significantly decreased the noradrenaline-stimulated BAT oxygen consumption expressed per microg DNA and per BAT pad, but did not change the basal oxygen consumption. Methimazole treatment significantly affected phospholipid content and phospholipid fatty acid composition. Among the major fatty acids of BAT, it decreased docosahexaenoic acid (DHA), arachidonic acid, palmitic acid, palmitoleic acid, and oleic acid, and it increased linoleic acid, stearic acid, and eicosapentaenoic acid. A regression analysis revealed a positive relationship between in vitro respiration and DHA levels in phospholipids (r = 0.404, p<0.05). These results suggest that thyroid hormones have trophic action on BAT and are necessary for BAT thermogenic activity. This study also suggests that DHA is involved in the regulation of BAT thermogenic activity, as we previously indicated.

Influence of Thyrotrophin-Releasing Hormone on Thermoregulation in Newborn Lambs

This study examined the effect of thyrotrophin-releasing hormone (TRH) administration on thermoregulation in the newborn. Twin lambs were either delivered near-term by caesarean section or born vaginally at term. Colonic temperature, O₂ consumption, CO₂ production, breathing and heart rates, plus plasma thyroid hormone and nonesterified fatty acid (NEFA) concentrations and thermogenic activity (i.e. GDP binding) of brown adipose tissue (BAT) were measured. In caesarean section delivered lambs colonic temperature decreased rapidly after birth, a response that was greater in the group designated for TRH treatment, in which colonic temperature fell to below 36.0°C at 80 min of life, prior to TRH administration. At this age colonic temperature had been restored to a mean of 38.70°C in controls. TRH had no influence on the composition or thermogenic activity of BAT. The incidence of shivering was not influenced by TRH, but treated lambs maintained a higher rate of O₂ consumption and ventilation compared with controls after colonic temperature had been restored to 38.56°C. TRH appeared to promote fat oxidation as O₂ consumption remained unchanged and CO₂ production declined by a greater rate in treated lambs, resulting in a lower respiratory quotient compared to controls. Heart rate and plasma concentrations of NEFA increased following TRH administration although this did not result in values greater than controls. Normothermic lambs born vaginally had BAT with a greater thermogenic activity, higher plasma thyroid hormone and NEFA concentrations compared with caesarean section delivered lambs, but a thermogenic response was not observed to TRH despite a rise in thyroid hormone concentrations. In conclusion, TRH can improve thermoregulation, an effect that could be linked to an increase in fat oxidation.

Diminished response to food deprivation of the rat brown adipose tissue mitochondrial uncoupling system with age.

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.

SWIMMING INCREASES COLD TOLERANCE IN YOUNG AND OLD MICE: WITH EMPHASIS ON BROWN ADIPOSE TISSUE 1204

Brown adipose tissue (BAT) expresses an unusual protein as uncoupling protein (UCP). Activation of UCP leads to the uncoupled passage of protons through the mitochondrial channel and the generation of heat. Currently, it is generally accepted that the impairment of BAT thermogenic activity with aging is a major cause for the decline of cold tolerance. Several studies have suggested, on the other hand, that, in addition to physical training, swimming training serves cold acclimation. The present study was, thus, undertaken to investigate the effect of swimming training on interscapular BAT activity in young and old mice. Both young and old mice (n = 62), aged 8 weeks and 26 months respectively, were divided into either the untrained groups or the trained groups. The trained mice underwent a 6-week swimming program (1 h/day, 5 days/week) in water at 35-36°C (to prevent hypothemia). Compared with young mice, the BAT mass was markedly smaller in old mice, accompanied by the decreased amount of UCP antigen, whereas there was no significant difference in the expression of UCP mRNA between young and old mice. Meanwhile, the swimming training significantly increased BAT mass and its protein content in both the young and old mice, suggesting hyperplasia. In addition, after the swimming training, the amounts of UCP antigen in both mice increased two to threefold over those of the respective untrained groups, while the expression of UCP mRNA did not vary substantially. Results on protein and guanosine 5′-diphosphate (GDP) binding (an index of UCP activity) in the mitochondria (means ± SEM) were: Table These findings indicate that swimming training enhances the nonshivering thermogenesis of BAT (irrespective of age), with resultant increases in tolerance to cold.

Responses of brown-adipose-tissue activity in the rat to 14 days of spaceflight

Abstract The current study was undertaken to investigate the effects of 14 days of spaceflight (SLS-2) on the function of brown adipose tissue (BAT) in male rats. The spaceflight did not seem to have any significant effect on BAT mass or its components (total protein, DNA, RNA, and triglyceride) in the animals ( n = 13). As compared with synchronous controls ( n = 8), the expression of uncoupling protein (UCP) mRNA in BAT of flight rats was enhanced considerably ( P g and came to the same degree 9 days later. Both UCP antigen and guanosine 5′-diphosphate (GDP)-binding values in the mitochondria recovered from BAT of flight rats increased three to four times over those of control rats 9 days after flight, being highly suggestive of an increase in the thermogenic activity of BAT, but not 6 h after flight. These data suggest that spaceflight itself may not have great influence on the function of BAT. Collectively the results suggest that samples, especially BAT, should be obtained in flight as well as after in order to avoid the influences of entry to space, and reentry and readaptation to 1 · g .

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.

Increased growth of brown adipose tissue but its reduced thermogenic activity in creatine-depleted rats fed β-guanidinopropionic acid

To study the responses of thermogenic activity in brown adipose tissue (BAT) to creatine depletion, male Wistar rats were fed creatine analogue β-guanidinopropionic acid (β-GPA) for about 10 weeks. Compared to control rats, a marked decrease in the levels of high-energy phosphates, such as phosphocreatine and ATP, was noted in BAT of β-GPA rats. Conversely, upward trends in other chemical components (DNA, glycogen, and total protein) in BAT as well as an increase in BAT mass were observed in β-GPA rats, suggesting a tendency to hyperplasia of the BAT. The thermogenic activity (which was assessed by guanosine 5′-diphosphate binding to BAT mitochondria) in the mitochondria recovered from BAT of β-GPA rats, however, was not increased in response to such changes but rather decreased. Moreover, uncoupling protein (UCP) content in the mitochondrial fraction of β-GPA rats was significantly lower than that in control rats (the relative amounts were 77 ± 6 and 100 ± 4%, respectively). Nevertheless, surprisingly, the level of UCP mRNA was remarkably greater in β-GPA rats than in control rats. These observations indicate that there is a discordance between BAT growth and activity in β-GPA rats, thereby suggesting that a failure on and after UCP translation may be involved in the impairment of BAT thermogenic activity with creatine depletion. The impairment of BAT thermogenic activity, that is, UCP activity may indicate that uncoupling or heat production was inhibited in order to increase the ATP synthesis in BAT of β-GPA rats in compensation for a reduction in the levels of high-energy phosphates (including ATP), with resultant hypothermia.

Exercise-training reduces BAT thermogenesis in rats

In the energy balance equation, physical activity represents one component of energy expenditure. From various studies it appears that exercise-training does not affect clearly thermogenesis which depends on brown adipose tissue (BAT) activity. In the present work we examine how exercise-training can influence food intake and body weight regulation in relation to BAT thermogenesis. The proton conductance of the uncoupling protein of BAT was examined in male adult Wistar trained 2 h/day for 20 days and compared to that of sedentary (2 h of fasting instead of exercise) or control animals. All animals were provided with separate sources of the 3 macronutrients (protein, fat and carbohydrate) containing an identical percentage of vitamins, salt mixture and cellulose powder. At the end of training, rat were placed at 5°C during 10 days, then during 4 days at 28°C. This condition has been demonstrated to favour and amplify BAT responsiveness to moderate modifications of stimulation. The body weight of trained rats became significantly lower than that of the control and sedentary rats and this difference persisted all throughout the experiment. When placed at 5°C, all rats increased their total ingestion: control rats enhanced fat intake, while sedentary and trained rats enhanced carbohydrate ingestion. When placed at 28°C, all rats had identical total energy and that of the 3 items intakes. BAT proton conductance was about 40% lower in the trained compared with the sedentary plus the control rats. This indicated a lower BAT thermogenic activity in the trained animals. It could be concluded that exercise-training in rats induces negative energy balance; the reduced BAT activity could restrain weight loss and overeating.

Potentiation of the anti‐obesity effect of the selective β3‐adrenoceptor agonist BRL 35135 in obese Zucker rats by exercise

1. The effects of chronic treatments with a selective beta 3-adrenoceptor agonist and a selective alpha 2-adrenoceptor antagonist and their interactions with physical exercise training were studied in experimental obesity. 2. BRL 35135 (beta 3-agonist, 0.5 mg kg-1 day-1 p.o.), atipamezole (alpha 2-antagonist, 4.0 mg kg-1 day-1 p.o.) and placebo were given to genetically obese male Zucker rats. Half of the rats were kept sedentary whereas the other half were subjected to moderate treadmill exercise training. Body weight gain, cumulative food intake, the neuropeptide Y content of the hypothalamic paraventricular nucleus, brown adipose tissue thermogenic activity (measured as GDP binding), plasma insulin and glucose levels were measured after 3 weeks' treatment and exercise. 3. Treatment with BRL 35135 reduced weight gain by 19%, increased brown adipose tissue thermogenic activity 45-fold and reduced plasma insulin by 50%. Atipamezole slightly increased food intake and neuropeptide Y content in the paraventricular hypothalamic nucleus but had no effect on the other measured parameters. Exercise alone had no effect on weight gain, food intake or thermogenic activity, whereas it reduced plasma insulin and glucose levels. 4. The effect of BRL 35135 on weight gain and thermogenic activity was significantly potentiated by exercise; the reduction in weight gain was 56% in comparison with 19% in sedentary animals. Food intake was significantly reduced in the BRL 35135-treated-exercise-trained animals, although neither beta 3-agonist nor exercise alone affected it. 5. Based on the present results in genetically obese Zucker rats, combination of 03-agonist treatment with a moderate physical training may offer a new feasible approach to the therapy of obesity.- BRL 35135; atipamezole; P3-adrenoceptor agonism; M2-adrenoceptor antagonism; brown adipose tissue; thermogenesis;genetic obesity; Zucker rat; exercise; neuropeptide Y

Effect of photoperiod on mitochondrial GDP binding and adenylate cyclase activity in brown adipose tissue of djungarian hamsters

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.

Effect of ambient temperature during 1st day of life on thermoregulation in lambs delivered by cesarean section

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.