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Author(s): P. Trayhurn [sup.1] [sup.2] Author Affiliations: (1) Obesity Biology Unit, University of Liverpool, Liverpool, UK (2) Clore Laboratory, University of Buckingham, Buckingham, UK Many whose research career has been [...]

Results of several studies have confirmed the presence of brown adipose tissue among health human adults. The results are also indicative of the fact that activated brown adipose tissue has the potential to contribute substantially to energy expenditure, and thus, may be further researched as a means of treating obesity.

The study aims to investigate brown adipose tissue activity in relation to body composition and energy metabolism among healthy men. The results indicate that there are a high percentage of men with such tissue and shows reduced activity among overweight or obese men, thereby indicating its use in the treatment of obesity.

As with other forms of psychological stress, conditioned fear causes an increase in body temperature. The mechanisms underlying this stress-induced hyperthermia are not well understood, but previous research suggests that nonshivering thermogenesis might contribute, as it does during cold exposure. The major source of nonshivering thermogenesis in the rat is brown adipose tissue (BAT), and the largest BAT deposit in that species is in the interscapular area just below the skin. BAT is also under sympathetic control via [beta]-adrenoceptors. If BAT contributes to fear-induced hyperthermia, then the interscapular skin should warm up faster than other skin areas, and this response should be suppressed by the [beta]-adrenoceptor antagonist, propranolol. We tested this noninvasively by infrared thermography. In conscious rats, 30 min of contextual fear caused hyperthermia (as indicated by a + 1.5[degrees]C increase in lumbar back skin temperature) and increased the difference in temperature between interscapular and lumbar back skin (TiScap - TBack) by + 1[degrees]C. Propranolol (10 mg/kg ip) completely abolished this hyperthermia; however, the TiScap-TBack increase was not reduced. In contrast, exposure to cold air (4[degrees]C) induced a +2.7[degrees]C increase in TiScap-TBack, which was reduced to +1[degrees]C after propranolol. The results show that conditioned fear-induced hyperthermia is of nonshivering origin and mediated by [beta]-adrenoceptors, but interscapular BAT does not contribute to it and does not appear to be activated, either. stress hyperthermia; thermoregulation; tail skin; freezing; sympathetic responses

The role of the tumor suppressor retinoblastoma protein (pRb) has been firmly established in the control of cell cycle, apoptosis, and differentiation. Recently, it was demonstrated that lack of pRb promotes a switch from white to brown adipocyte differentiation in vitro. We used the Cre-Lox system to specifically inactivate pRb in adult adipose tissue. Under a high-fat diet, pRb-deficient ([pRb.sup.ad-/-]) mice failed to gain weight because of increased energy expenditure. This protection against weight gain was caused by the activation of mitochondrial activity in white and brown fat as evidenced by histologic, electron microscopic, and gene expression studies. Moreover, [pRb.sup.-/-] mouse embryonic fibroblasts displayed higher proliferation and apoptosis rates than [pRb.sup.+/+] mouse embryonic fibroblasts, which could contribute to the altered white adipose tissue morphology. Taken together, our data support a direct role of pRb in adipocyte cell fate determination in vivo and suggest that pRb could serve as a potential therapeutic target to trigger mitochondrial activation in white adipose tissue and brown adipose tissue, favoring an increase in energy expenditure and subsequent weight loss. brown adipose tissue | mitochondria | pocket proteins | obesity

The activity of brown adipose tissue (BAT), a site of nonshivering metabolic thermogenesis, has been reported to increase after interleukin (IL)-1[beta]/lipopolysaccharide injection. To clarify the possible contribution of BAT thermogenesis to whole body febrile response, we investigated febrile and thermogenic response to IL-1[beta] using mice deficient in uncoupling protein-1 (UCP1), a key molecule for BAT thermogenesis. In wild-type (WT) mice, IL-1[beta] injection (5 [micro]g/kg ip) increased body temperature (+ 1.82[degrees]C at 20 min), decreased physical activity (-37% at 1 h), and produced a slight and insignificant rise (+15% at 1 h) in oxygen consumption ([Vo.sub.2]). [Vo.sub.2] dependent on metabolic thermogenesis ([DELTA][Vo.sub.2] thermogenesis) calculated by correcting the effect of physical activity was increased after IL-1[beta] injection (726 [+ or -] 200 ml*[h.sup.-1]*[kg.sup.-1] at 1 h). Almost the same responses were observed in UCP1-deficient mice, showing 638 [+ or -] 87 ml*[h.sup.-1]*[kg.sup.-1] of [DELTA] [Vo.sub.2] thermogenesis at 1 h. In contrast, CL316,243, a selective activator of BAT thermogenesis, increased body temperature, decreased physical activity, and produced a significant rise in [Vo.sub.2] in WT mice, showing 1,229 [+ or -] 35 ml*[h.sup.-l]*[kg.sup.-1] of A [DELTA] [Vo.sub.2] thermogenesis at 1 h. These changes were not observed in UCP1-deficient mice. These results, conflicting with a previously proposed idea of a role of BAT in fever, suggest a minor contribution of BAT thermogenesis to IL-1 [beta]-induced fever. In support of this, we found no effect of IL- 1 [beta] on triglyceride content and UCP1 mRNA level in BAT, in contrast with apparent effects of CL316,243. uncoupling protein-1; oxygen consumption; body temperature; knockout mouse; intedeukin-1[beta]

C57BL/6 (B6) mice subjected to a high-fat diet develop metabolic syndrome with obesity, hyperglycemia, and insulin resistance, whereas 129S6/SvEvTac (129) mice are relatively protected from this disorder because of differences in higher basal energy expenditure in 129 mice, leading to lower weight gain. At a molecular level, this difference correlates with a marked higher expression of uncoupling protein 1 (UCP1) and a higher degree of uncoupling in vitro in mitochondria isolated from muscle of 129 versus B6 mice. Detailed histological examination, however, reveals that this UCP1 is in mitochondria of brown adipocytes interspersed between muscle bundles. Indeed, the number of UCP1-positive brown fat cells in intermuscular fat in 129 mice is >700-fold higher than in B6 mice. These brown fat cells are subject to further up-regulation of UCP1 after stimulation with a [[beta].sub.3]-adrenergic receptor agonist. Thus, ectopic deposits of brown adipose tissue in intermuscular depots with regulatable expression of UCP1 provide a genetically based mechanism of protection from weight gain and metabolic syndrome between strains of mice. brown fat | UCP1 | diabetes | genetics | obesity

Survival of organisms requires the ability to adapt to changes in the environment. Adaptation of oxidative metabolism is essential for meeting increased energy demands in response to stressors, such as exposure to cold temperatures or increased physical activity. Adaptive changes in metabolism are often achieved at the level of gene expression, and nuclear receptors have prevalent roles in mediating such responses. Estrogen-related receptor [alpha] (ERR[alpha]) was the first orphan nuclear receptor to be identified, and yet its physiologic function remains unknown. Here, we show that mice lacking ERR[alpha] are unable to maintain body temperature when exposed to cold. Surprisingly, the inability to adapt to cold is not due to defects in the acute transcriptional induction of genes important for thermogenesis. Rather, we show that ERR[alpha] is needed for the high levels of mitochondrial biogenesis and oxidative capacity characteristic of brown adipose tissue (BAT), and thus for providing the energy necessary for thermogenesis. ERR[alpha] fulfills this role by acting directly at genes important for mitochondrial function, parallel to other factors controlling mitochondrial gene expression, such as NRF1 and NRF2/GABPA. Our findings demonstrate that ERR[alpha] is a key regulator of mitochondrial biogenesis and oxidative metabolism, and essential for adaptive thermogenesis. mitochondrial biogenesis | oxidative metabolism | brown adipose tissue

Control of mitochondrial biogenesis in brown adipose tissue (BAT), as part of the thermogenesis program, is a complex process that requires the integration of multiple transcription factors to orchestrate mitochondrial and nuclear gene expression. Despite the knowledge of the role of sex hormones on BAT physiology, little is known about the effect of these hormones on the mitochondrial biogenic program. The aim of this study was to determine the effect of testosterone, 17[beta]estradiol, and progesterone on the expression of nuclear factors involved in the control of mitochondrial biogenesis and thermogenic function such as ppar[gamma], pgc1[alpha], nrf1, gabpa, and tfam, and also an inhibitor of PI3K-Akt pathway, recently found to be involved in the control of mitochondrial recruitment (pten). For this purpose, an in vitro assay using cell-cultured brown adipocytes was used to address the role of steroid hormones, progesterone, testosterone, and 17[beta]-estradiol on the mRNA expression of these factors by real-time PCR. Thus 17[beta]-estradiol seemed to exert a dual effect, activating the PI3K-Akt pathway by inhibiting pten mRNA expression and also inhibiting nrfl and tram mRNA expression. Progesterone seemed to positively stimulate mitochondriogenesis and BAT differentiation by increasing the mRNA expression of the gabpa-tfam axis and ppar[gamma], respectively, but also exerted a negative output by increasing pten mRNA levels. Finally, testosterone inhibited the transcription of pgc1[alpha], the master factor involved in UCP1 expression and mitochondrial biogenesis. In conclusion, our results support the idea that sex hormones have direct effects on different mediators of the mitochondriogenesis program. brown adipose tissue; sex steroids; mitochondriogenesis program signaling; nuclear and mitochondrial transcription factors

Serotyping and a multilocus sequence typing (MLST) scheme, based on the sequencing of three genes (fimA, manB, and mdh), are used to characterize the human and bovine clinical Salmonella isolates obtained from across New York state over the course of 1 year. The results have shown that cattle might be a reservoir for many of the common human disease-associated serotypes and sequence type (ST) that are not associated with avian hosts.

In cold defense and fever, activity increases in sympathetic nerves supplying both tail vessels and interscapular brown adipose tissue (iBAT). These mediate cutaneous vasoconstrictor and thermogenic responses, respectively, and both depend upon neurons in the rostral medullary raphr. To examine the commonality of brain circuits driving these two outflows, sympathetic nerve activity (SNA) was recorded simultaneously from sympathetic fibers in the ventral tail artery (tail SNA) and the nerve to iBAT (iBAT SNA) in urethane-anesthetized rats. From a warm baseline, cold-defense responses were evoked by intermittently circulating cold water through a water jacket around the animal's shaved trunk. Repeated episodes of trunk skin cooling decreased core (rectal) temperature. The threshold skin temperature to activate iBAT SNA was 37.3 [+ or -] 0.5[degrees]C (n = 7), significantly lower than that to activate tail SNA (40.1 [+ or -] 0.4[degrees]C; P < 0.01, n = 7). A fall in core temperature always strongly activated tail SNA (threshold 38.3 [+ or -] 0.2[degrees]C, n = 7), but its effect on iBAT SNA was absent (2 of 7 rats) or weak (threshold 36.9 [+ or -] 0.1[degrees]C, n = 5). The relative sensitivity to core vs. skin cooling (K-ratio) was significantly greater for tail SNA than for iBAT SNA. Spectral analysis of paired recordings showed significant coherence between tail SNA and iBAT SNA only at 1.0 [+ or -] 0.1 Hz. The coherence was due entirely to the modulation of both signals by the ventilatory cycle because it disappeared when the coherence spectrum was partialized with respect to airway pressure. These findings indicate that independent central pathways drive cutaneous vasoconstrictor and thermogenic sympathetic pathways during cold defense. tail; vasoconstrictor fiber; interscapular brown adipose tissue; spectral analysis doi:10.1152/ajpregu.00850.2005.

Participation of brown adipose tissue [through the action of the uncoupling protein-1 (UCP1)] in adaptive adrenergic nonshivering thermogenesis is recognized, but the existence of a response to adrenergic stimulation in UCP1-ablated mice implies that a mechanism for an alternative adaptive adrenergic thermogenesis may exist. Here, we have used UCP1-ablated mice to examine the existence of an alternative adaptive adrenergic nonshivering thermogenesis, examined as the oxygen consumption response to systemically injected norepinephrine into anesthetized or conscious mice acclimated to different temperatures. We confirm that UCP1-dependent adrenergic nonshivering thermogenesis is adaptive, but we demonstrate that the adrenergic UCP1-independent thermogenesis is not recruitable by cold acclimation. Thus, at least in the mouse, no other proteins or enzymatic pathways exist that can participate in or with time take over the UCP1 mediation of adaptive adrenergic nonshivering thermogenesis, even in the total absence of UCP1. UCP1 is thus the only protein capable of mediating cold acclimation-recruited adaptive adrenergic nonshivering thermogenesis. uncoupling protein-1; brown adipose tissue; norepinephrine; oxygen consumption; muscle thermogenesis; basal metabolic rate doi:10.1152/ajpendo.00387.2005

With the recent advances in high-throughput genotyping techniques, it is now possible to perform whole-genome association studies to fine map causal polymorphisms underlying important traits that influence susceptibility to human diseases and efficacy of drugs. Once a genome scan is completed the results can be sorted by the association statistic value. What is the probability that true positives will be encountered among the first most associated markers? When a particular polymorphism is found associated with the trait, there is a chance that it represents either a 'true' or a 'false' association (TA vs. FA). Setting appropriate significance thresholds has been considered to provide assurance of sufficient odds that the associations found to be significant are genuine. However, the problem with genome scans involving thousands of markers is that the statistic values of FAs can reach quite extreme magnitudes. In such situations, the distributions corresponding to TAs and the most extreme FAs become comparable and significance thresholds tend to penalize TAs and FAs in a similar fashion, when sorting between true and false associations, the 'typical' place (i.e., rank) of TAs among the most significant outcomes becomes important, ordered by the association statistic value. The distribution of ranks that we study here allows calculation of several useful quantities. In particular, it gives the number of most significant markers needed for a follow-up study to guarantee that a true association is included with certain probability. This can be calculated conditionally on having applied a multiple-testing correction. Effects of multilocus (e.g., haplotype association) tests and impact of linkage disequilibrium on the distribution of ranks associated with TAs are evaluated and can he taken into account.

The expression of the Elovl3 gene, which belongs to the Elovl gene family coding for microsomal enzymes involved in very long-chain fatty acid (VLCFA) elongation, is dramatically increased in mouse brown adipose tissue upon cold stimulation. In the present study, we show that the cold-induced Elovl3 expression is under the control of peroxisome proliferator-activated receptor-[alpha] (PPAR[alpha]) and that this regulation is part of a fundamental divergence in the regulation of expression for the different members of the Elovl gene family. In cultured brown adipocytes, a mixture of norepinephrine, dexamethasone, and the PPAR[alpha] ligand Wy-14643, which rendered the adipocytes a high oxidative state, was required for substantial induction of Elovl3 expression, whereas the same treatment suppressed Elovl1 mRNA levels. The nuclear liver X receptor (LXR) has been implicated in the control of fatty acid synthesis and subsequent lipogenic processes in several tissues. This regulation is also exerted in part by sterol regulatory element-binding protein (SREBP-1), which is a target gene of LXR. We found that stimulation of Elovl3 expression was independent of LXR and SREBP-1 activation. In addition, exposure to the LXR agonist TO-901317 increased nuclear abundance of LXR and mature SREBP-1 as well as expression of the elongases Lce and Elovl1 in a lipogenic fashion but repressed Elovl3 expression. A functional consequence of this was seen on the level of esterified saturated fatty acids, such as C22:0, which was coupled to Elovl3 expression. These data demonstrate differential transcriptional regulation and concomitantly different functional roles for fatty acid elongases in lipid metabolism of brown adipocytes, which reflects the metabolic status of the cells. elongase; brown adipose tissue; gene expression; very long-chain fatty acid

Stearoyl-CoA desaturase (SCD) catalyzes the synthesis of oleate (C18:1) and palmitoleate (C16:1), which are the main monounsaturated fatty acids of membrane phospholipids, triglycerides, wax esters, and cholesterol esters. Previously, we showed that SCD1 deficiency elevates insulin-signaling components and downregulates protein-tyrosine phosphatase-1B (PTP-1B) in muscle, a major insulin-sensitive tissue. Here we found that, in brown adipose tissue (BAT), another insulin-sensitive tissue, the basal tyrosine phosphorylations of insulin receptor (IR) and IR substrates (IRS-1 and IRS-2) were upregulated in SCD[1.sup.-/-] mice compared with wild-type mice. The association of IRS-1 and IRS-2 with the [alpha]-p85 subunit of phosphatidylinositol 3-kinase as well as Akt-[Ser.sup.473] and Akt-[Thr.sup.308] phosphorylation is also elevated in the SCD[1.sup.-/-] mice. The mRNA expression, protein levels, and activity of PTP-1B implicated in the attenuation of the insulin signal are reduced in the SCD[1.sup.-/-] mice. The content of GLUT4 in the plasma membrane increased 2.5-fold, and this was accompanied by a 6-fold increase in glucose uptake in BAT of SC[D.sup.1-/-] mice. The increased glucose uptake was associated with higher glycogen synthase activity and glycogen accumulation. In the presence of insulin, [U-[sup.14]C]glucose incorporation into glycogen was increased in BAT of SCD[1.sup.-/-] mice. Taken together, these studies illustrate increased insulin signaling and increased glycogen metabolism in BAT of SCD[1.sup.-/-] mice. stearoyl-coenzyme A desaturase; brown adipose tissue; insulin signaling

The responses to cold and the thermogenic activity of the FOK rat (FOK), a genetically heat-tolerant strain with a capacity for enhanced heat loss, were compared with those of Wistar King A/H and Std:Wistar strains. The FOK strains were observed to have higher capacity for nonshivering thermogenesis despite of their high capacity for heat tolerance. This is speculated to be a result of an increase use of lipids and improvement in the circulation of the brown adipose tissue.

The effects of intracerebroventricular protaglandin E2 (PGE2) in rats during gestation were investigated to determine whether suppression of PGE2-induced fever at near term is due to enhanced vasopressin-induced antipyresis. A transient but profound decrease in the sympathetic response to central PGE2 at near term was observed. Results also suggested that fever reduction at near term is not related with enhanced vasopressin antipyresis, but may be due to a reduced sympathetic drive to the interscapular brown adipose tissue.

A study was conducted to find out if cold exposure controls norepinephrine (NE) uptake transporter (NET). Kinetic parameters for [3H]NE uptake and [3H]nisoxetine (Nis) binding were determined in rat interscapular brown adipose tissue (ISBAT) from seven-day exposed (CE) and control rats. Findings illustrate that the ISBAT NET is downregulated after cold exposure. Decreases in ISBAT NET content precede changes in NET density. However, plasma NE content is not affected by regulation of the NET.

Research was conducted to reexamine the physiological role of monocarboxylate transport in brown adipose tissue mitochondria. Phenylpyruvate, pyruvate and alpha-ketoisovalerate uniport were tested using the uncoupling protein as a GDP-sensitive swelling in K+ salts induced by valinomycin or by monensin and carbonyl cyanide-p-(trifluoromethoxy)phenylhydrazone in Na+ salts. Results indicate that pyruvate cycling might contribute partially to the overall thermogenesis but should be essential in the fine control of coupling.

Involuntary energy expenditure may contribute to obesity. Uncoupling proteins may may play a significant role in the the expenditure and regulation of energy balance. Further research will determine if obesity can be explained by variations in the uncoupling protein gene family.

Research was conducted to test whether the selective beta3-adrenergic agonist CL-316243 can emulate the beneficial effects of cold exposure in lean and obese ZDF/Gmi-fa male rats, a new model of type II diabetes. Results showed that chronic CL treatment enhances glucose tolerance and insulin responsiveness in obese ZDF rats by a mechanism similar to that induced by chronic cold exposure.

The respiratory and lipolytic effects of adrenergic agonists and antagonists were investigated in rat brown adipocytes to determine the physiologic functions of beta1-, beta2- and beta3-adrenoreceptors (ARs). Beta-agonists stimulated both lipolysis and respiration 8-10 times above basal levels. Norepinephrine was able to stimulate lipolysis and respiration through beta1-ARs while beta2-ARs played only a minor role in this mechanism. Meanwhile, beta3-ARs may represent the physiological receptors for high norepinephrine concentrations.

Research was conducted to examine the effect of triiodothyronine (T3) administration to euthyroid rats on Beta3-adrenoceptor (Beta3-AR) expression and on the different components of the adenylyl cyclase system in brown adipose tissue. In rats treated with T3, the Beta3-AR density (assessed by the binding of [3H]CGP-12177) showed a decrease of 50%, as did their mRNA, as analyzed by reverse transcriptase-polymerase chain reaction. Results indicate that downregulation of the Beta3-AR by T3 was counterbalanced by changes in other components of the AC cascade.

Brown fat cells were tested for ATP responses to show that cytosolic calcium levels were increased by ATP through release from intracellular stores and through influx. Micromolar concentrations of extracellular ATP had a number of effects on brown adipocytes. ATP indirectly activated a nonselective cation conductance that was independent of cytosolic calcium levels in patch voltage-clamped brown fat cells. The myriad responses to extracellular ATP indicate that P2 receptor-mediated signaling is important in brown adipocyte physiology.

The effect of the removal of the carboxyl group of E190 in the production of uncoupling protein (UCP), with decreased or without control of nucleotide binding was investigated through mutation of glutamic acid 190 into glutamine of UCP expressed in yeasts. Results have shown that the removal of carboxyl group by conversion of glutamic acid 190 into glutamine enhanced the binding affinity at pH >6.9. It was shown that E190 influenced the pH control of both H+ and Cl- transport.

Woodward reagent K (WRK) was applied to the uncoupling protein (UCP) to prove the hypothesis that the transport inhibiting nucleotide binding to the UCP is regulated by the dissociation state of a carboxyl group in UCP with pK 4.5, and to identify the carboxyl group. Findings indicated that the pH-sensing carboxyl group controls both the nucleoside di- and triphosphate binding. Acid residue E190 found in the fourth transmembrane helix was identified as the carboxyl group.

Uncoupling protein (UCP) from brown adipose tissue mitochondria reconstituted into giant liposomes was found to exhibit stable chloride channel behavior under patch-clamp conditions. Also, the effects on the channel characteristics of various potential factors were studied for the sake of comparison with the Cl- transport activity. The anion channel showed by UCP under these conditions showed Cl- fluxes many order of magnitude higher than the carrier-type Cl- transport activity previously reported.

The relationships between the two-stage nucleotide binding and the inhibition of the H+ transport activity in reconstituted proteoliposomes were studied. Limited tryptic digestion was utilized as an indicator of conformational change caused by the nucleotide binding in the isolated protein. Findings indicated that the uncoupling protein from brown adipose tissue mitochondria can exist in a loose noninhibited and tight inhibited conformational state. The equilibrium between these two conformations is shifted to the tight state with unsubstituted nucleotides but remains to various degrees in the loose state with 2'-O-dansyl and dimethylaminonaphthoyl derivatives.

Both norepinephrine and insulin exert direct growth effects or trophic actions in mouse brown adipocytes, with larger effects of the former than the latter. The function of insulin-like growth factor is unclear as saturating concentrations have no effect on protein turnover. Succinate dehydrogenase content and cell recovery show improvement, after a fast, in the presence of norepinephrine in mouse brown adipocytes. Norepinephrine effects are inhibited by propranolol.

Short-term exposure to thermoneutrality produces a decrease in brown adipose tissue (BAT), uncoupling protein (UCP) mRNA levels in rats. The hypothalamic neuropeptide Y (NPY) activity remains unchanged. Small exposures to thermoneutrality are unable to stimulate the hypothalamic NPY system, suggesting that the mechanisms responsible for BAT activity inhibition are other than those involving NPY. Stimulation of the NPYergic arcuatoparaventricular system in a thermonuclear environment with low energies, probably, mediates the decrease in BAT levels.

The adrenergic depolarization of conductance in brown adipocytes is due to an increase in the intracellular calcium which stimulates a chloride-sensitive conductance. This conductance is different from the volume-sensitive chloride conductance of the cell. Cytoplasmic factors and intracellular calcium affect this chloride conductance. Cells cultured for short periods show depolarization of conductance more than those cultured for longer periods.

Intracerebroventricular injection of the nitric oxide synthesis inhibitor L-NAME decreases food intake and in enhances the oxygen consumption, the firing rate of sympathetic nerves innervating interscapular brown adipose tissue and temperature. However, intraperitoneal injection decreased all the factors. Different effects of the molecule on sympathetic output are most likely responsible for the oppositional effects when the different injection routes were used.

A study of the influence of corticosterone on Brown adipose tissue (BAT) thermogenic activity and lipid storage in adrenalectomized rats by examining them after 5 days of corticosterone administration reveals that corticosteroid suppresses nonshivering thermogenesis and enhances lipid storage. BAT thermogenic attributes are severely influenced by corticosterones. Adrenalectomy enhances BAT DNA while all doses of corticosterone retain BAT DNA at intact levels. Increased corticosterone levels increase the size and number of liquid droplets within BAT adipocytes.

A study of old rats reveals dissonance between uncoupling protein (UCP) expression and brown adipose tissue (BAT) thermogenic activity. This suggests that aging may be associated with failure during or after UCP translation, leading to impaired BAT thermogenic activity. Age-related changes in insulin receptor and glucose transporter-4 mRNA levels may also be involved in the process.

Studies on brown adipose tissue response to hypothalamic stimulation in rats suggests that the initial phase 1 reduction in interscapular brown adipose tissue temperature (IBAT) is mediated through dopaminergic pathways. Amphetamine injections to the intracerebroventricular regions produce reduced IBAT temperatures resembling phase 1 phenomena. The injection of pimozide suppresses phase 1, reinforcing the role of dopaminergic mechanisms in the process.

The nervous activity (SNA) to interscapular brown adipose tissue (IBAT) in old mice was measured and it was compared with that of adult mice to find if old male C57BL/6J mice produce less heat during cold weather. IBAT-SNA was more in old mice than in adults because of inadequate insulation, as old mice have lesser body weight and lesser TCO, and very little difference in metabolic heat production at 22 degrees Celsius.

Hypothyroid brown adipose tissues (BAT) were examined in Sprague-Dawley rats to understand the processes that induce a rise in lipogenesis. Lipogenesis in hypothyroid BAT was lowered to euthyroid degrees when the animals were kept at 28 degrees Celsius. In hypothyroid BAT, a 90% decrease in lipogenesis to less than in euthyroid tissue resulted from denervation. The decrease in the metabolic rate in these animals is countered by the sympathetic nervous system mediating the enhancement in BAT lipogenesis, observed for hypothyroidism.

The glucose uptake brown adipose tissue (BAT) increases considerably by exposure to cold. The brown adipose tissue (BAT) is the primary site for the sympathetically controlled metabolic heat manufacture. Rats exposed to cold for different periods were examined and the relationship between glucose uptake and glucose transporters (GLUT) was determined. Cold exposure increases the glucose intake by an increase in the GLUT-4 amount, caused by the de novo synthesis simulation and an increase in the GLUT-4 synthesis without simulation.

The findings from the research on the vascular endothelial growth factor B (VEGFB) produced by heart, skeletal muscle and brown adipose tissue and novel role of VEGFB as a regulator of lipid delivery to fat-burning tissues. The study could have important implications for indisputable evidence of profound influence of lipid balance at the whole-body and tissue levels on interorgan crosstalk and possible application of VEGFB as therapeutic target.

The research related to a common origin of white and brown adipocytes and questions regarding the provenance and regulation of brown adipose tissue which facilitates the recruitment of brown fat cells in the treatment of obesity is reviewed. The findings from the research related to functional brown adipose tissue in adults indicated that Myf5-negative brown cells play a significant role in the regulation of human energy expenditure.

A study was conducted to investigate the patterns of landscape genetic structures in North American river otters (Lontra canadensis) using georeferenced multilocus microsatellite genotypes in spatially implicit (STRUCTURE) and spatially explicit (GENELAND) models. Findings reveal that all models identified 3 subpopulations of river otters in Lousiana