Brown Adipose Tissue Protein Research Articles

The expression of Muscle ankyrin repeat proteins in brown adipose tissue

MARP family members CARP, Ankrd2 and DARP are expressed in the striated muscle, while DARP protein is also detected in brown adipose tissue (BAT). Taking into account recent findings concerning the common origin of muscle and brown fat, expression of CARP and Ankrd2 in mouse BAT was investigated. We demonstrated Ankrd2 expression in both inactive and thermogenically active BAT, while CARP expression was not detected. Our findings suggest that the expression of Ankrd2 in BAT could be a part of the ?myogenic transcriptional signature?, further supporting the evidence that muscle and brown adipose cells arise from the same myoblastic precursor.

Brd2 disruption in mice causes severe obesity without Type 2 diabetes

Certain human subpopulations are metabolically healthy but obese, or metabolically obese but normal weight; such mutations uncouple obesity from glucose intolerance, revealing pathways implicated in Type 2 diabetes. Current searches for relevant genes consume significant effort. We have reported previously a novel double bromodomain protein called Brd2, which is a transcriptional co-activator/co-repressor with SWI/SNF (switch mating type/sucrose non-fermenting)-like functions that regulates chromatin. In the present study, we show that wholebody disruption of Brd2, an unusual MHC gene, causes lifelong severe obesity in mice with pancreatic islet expansion, hyperinsulinaemia, hepatosteatosis and elevated pro-inflammatory cytokines, but, surprisingly, enhanced glucose tolerance, elevated adiponectin, increased weight of brown adipose tissue, heat production and expression of mitochondrial uncoupling proteins in brown adipose tissue, reduced macrophage infiltration in white adipose tissue, and lowered blood glucose, leading to an improved metabolic profile and avoiding eventual Type 2 diabetes. Brd2 is highly expressed in pancreatic beta-cells, where it normally inhibits beta-cell mitosis and insulin transcription. In 3T3-L1 pre-adipocytes, Brd2 normally co-represses PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) and inhibits adipogenesis. Brd2 knockdown protects 3T3-L1 adipocytes from TNF-alpha (tumour necrosis factor-alpha)-induced insulin resistance, thereby decoupling inflammation from insulin resistance. Thus hypomorphic Brd2 shifts energy balance toward storage without causing glucose intolerance and may provide a novel model for obese metabolically healthy humans.

S5/1 Control of the synthesis of uncoupling and coupling proteins in brown adipose tissue

S5/1 Control of the synthesis of uncoupling and coupling proteins in brown adipose tissue

Integration of DIGE and Bioinformatics Analyses Reveals a Role of the Antiobesity Agent Tungstate in Redox and Energy Homeostasis Pathways in Brown Adipose Tissue

Our previous results demonstrated that tungstate decreased weight gain and adiposity in obese rats through increased thermogenesis and lipid oxidation, suggesting that brown adipose tissue was one of the targets of its antiobesity effect. To identify potential targets of tungstate, we used DIGE to compare brown adipose tissue protein extracts from the following experimental groups: untreated lean, tungstate-treated lean, untreated obese, and tungstate-treated obese rats. To distinguish direct targets of tungstate action from those that are secondary to body weight loss, we also included in the analysis an additional group consisting of obese rats that lose weight by caloric restriction. Hierarchical clustering of analysis of variance and t test contrasts clearly separated the different experimental groups. DIGE analysis identified 20 proteins as tungstate obesity direct targets involved in Krebs cycle, glycolysis, lipolysis and fatty acid oxidation, electron transport, and redox. Protein oxidation was decreased by tungstate treatment, confirming a role in redox processes; however, palmitate oxidation, as a measure of fatty acid beta-oxidation, was not altered by tungstate, thus questioning its putative function in fatty acid oxidation. Protein network analyses using Ingenuity Pathways Analysis highlighted peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) as a potential target. We confirmed by real time PCR that indeed tungstate up-regulates PGC-1alpha, and its major target, uncoupling protein 1, was also increased as shown by Western blot. These results illustrate the utility of proteomics and bioinformatics approaches to identify targets of obesity therapies and suggest that in brown adipose tissue tungstate modulates redox processes and increases energy dissipation through uncoupling and PGC-1alpha up-regulation, thus contributing to its overall antiobesity effect.

Antioxidant defense in hibernation: Cloning and expression of peroxiredoxins from hibernating ground squirrels, Spermophilus tridecemlineatus

Mammalian hibernation is characterized by prolonged torpor bouts interspersed by brief arousal periods. Adequate antioxidant defenses are needed both to sustain cell viability over weeks of deep torpor and to defend against high rates of oxyradical formation associated with massive oxygen-based thermogenesis during arousal. The present study shows that up-regulation of peroxiredoxins contributes to antioxidant defense during torpor in thirteen-lined ground squirrels, Spermophilus tridecemlineatus. Expression levels of three isozymes of the 2-Cys peroxiredoxin (Prdx) family were quantified by Western blotting, the results showing 4.0- and 12.9-fold increases in Prdx1 protein in brown adipose tissue (BAT) and heart, respectively, during hibernation compared with euthermia. Comparable increases in Prdx2 were 2.4- and 3.7-fold whereas Prdx3 rose by 3.1-fold in heart of torpid animals. Total 2-Cys peroxiredoxin enzymatic activity also rose during hibernation by 1.5-fold in heart and 3.5-fold in BAT. Furthermore, RT-PCR showed that prdx2 mRNA levels increased by 1.7- and 3.7-fold in BAT and heart, respectively, during hibernation. A partial nucleotide sequence of prdx2 from ground squirrels was obtained by PCR amplification, the deduced amino acid sequence showing 96–97% identity with Prdx2 from other mammals. Some unique amino acid substitutions were identified that might contribute to stabilizing Prdx2 conformation at the near 0 °C body temperatures during torpor.

Ghrelin affects gastrectomy-induced decrease in UCP1 and β 3-AR mRNA expression in mice

In this study we investigated the effects of gastrectomy (Gx) and of the gastric hormone, ghrelin, on the expression of proteins in brown adipose tissue (BAT) that are thought to be involved in thermogenesis. Heat production in BAT is known to depend upon activation and increased expression of β 3-adrenergic receptors (β 3-AR) and the consequent up-regulation of uncoupling protein 1 (UCP1). Mice were subjected to Gx or sham operation. One week later they started to receive daily subcutaneous injections of either saline or ghrelin (12 nmol) for two or eight weeks. Neither Gx nor ghrelin affected daily food intake. Gx did not lower body weight gain (except during the first post-operative week) but Gx mice responded to eight weeks of ghrelin treatment with a greater body weight increase (37%, p < 0.05) than saline-injected Gx mice; sham-operated mice did not respond to ghrelin. Gx resulted in a greatly reduced expression of both UCP1 and β 3-AR mRNA in BAT (50% reduction or more, p < 0.01) compared to sham-operated mice. Eight weeks of ghrelin treatment raised the UCP1 as well as the β 3-AR mRNA expression in the Gx mice, whereas two weeks of ghrelin treatment decreased UCP1 and β 3-AR mRNA expression compared to Gx mice receiving saline. In fact, mRNA expression in Gx mice after treatment with ghrelin for eight weeks was similar to that in saline-treated sham-operated mice. Ghrelin did not affect UCP1 and β 3-AR mRNA in sham-operated mice neither two nor eight weeks after the operation. The results suggest 1) that signals from the stomach stimulate BAT UCP1 (and possibly thermogenesis) and 2) that ghrelin may contribute to the control of UCP1 expression.

Remodeling of White Adipose Tissue after Retinoic Acid Administration in Mice

A reduced brown adipose phenotype in white adipose tissue (WAT) may contribute to obesity and type 2 diabetes in humans. Retinoic acid, the carboxylic form of vitamin A, triggers in rodents a reduction of body weight and adiposity and an increased expression of uncoupling proteins in brown adipose tissue and skeletal muscle. In this study, we investigated possible remodeling effects of all-trans retinoic acid (ATRA) in WAT depots. Changes in the expression of genes related to thermogenesis and fatty acid oxidation and levels of phosphorylated retinoblastoma protein were analyzed in WAT depots of adult NMRI male mice acutely injected with ATRA or vehicle, together with biometric and blood parameters. Body fat loss after ATRA treatment was unaccompanied by any increase in circulating nonesterified fatty acids or ketone bodies and accompanied by increased rectal temperature. The treatment triggered an up-regulation of the mRNA levels of uncoupling proteins 1 and 2, peroxisome proliferator-activated receptor gamma coactivator-1alpha, peroxisome proliferator-activated receptor alpha, muscle- and liver-type carnitine palmitoyltransferase 1, and subunit II of cytochrome oxidase in different WAT depots. Levels of phosphorylated retinoblastoma protein in WAT depots were increased after ATRA treatment. Adipocyte size was reduced, and the number of multilocular adipocytes was increased in inguinal WAT of ATRA-treated mice. The results indicate that ATRA favors the acquisition of brown adipose tissue-like properties in WAT. Understanding the mechanisms and effectors involved in the remodeling of WAT can contribute to new avenues of prevention and treatment of obesity and type 2 diabetes.

Differential induction of genes in liver and brown adipose tissue regulated by peroxisome proliferator-activated receptor-α during fasting and cold exposure in acyl-CoA dehydrogenase-deficient mice

Mice deficient for either long-chain acyl-CoA dehydrogenase (LCAD−/−) or very-long-chain acyl-CoA dehydrogenase (VLCAD−/−) develop hepatic steatosis upon fasting, due to disrupted mitochondrial fatty acid oxidation. Moreover, neither mouse model can maintain core body temperature when exposed to cold. We investigated the effects of fasting and cold exposure on gene expression in these mice. Non-fasted LCAD−/− mice showed gene expression changes indicative of fatty liver, including elevated mRNA levels for peroxisome proliferator-activated receptor-γ (PPARγ) and genes involved in lipogenesis. In LCAD−/− and VLCAD−/− mice challenged with fasting and cold exposure, expression of fatty acid oxidation genes was elevated in liver, consistent with increased PPARα activity. This effect was not seen in brown adipose tissue, suggesting that expression of these genes may be regulated differently than in liver. The effect of acute cold exposure on expression of fatty acid oxidation genes was measured in peroxisome proliferator-activated receptor (PPAR)-α-deficient mice (PPARα−/−) and controls. In PPARα−/− mice, basal expression of the acyl-CoA dehydrogenases was reduced in liver but was not altered in brown adipose tissue. While cold altered the expression of PPARγ, sterol-regulatory element binding protein-1 (SREBP-1), ATP citrate lyase, and the uncoupling proteins in brown adipose tissue from both PPARα−/− and control mice, fatty acid oxidation genes were unaffected. Thus, while fatty acid oxidation appears critical for non-shivering thermogenesis, expression of the acyl-CoA dehydrogenases is not influenced by cold exposure. Moreover, mitochondrial fatty acid oxidation genes are not regulated by PPARα in brown adipose tissue as they are in liver.

Short-term resistance to diet-induced obesity in A/J mice is not associated with regulation of hypothalamic neuropeptides.

To investigate the mechanisms underlying long-term resistance of the A/J mouse strain to diet-induced obesity, we studied, over a period of 4 wk, the expression of uncoupling proteins in brown adipose tissue and the expression of hypothalamic neuropeptides known to regulate energy homeostasis and then used microarray analysis to identify other potentially important hypothalamic peptides. Despite increased caloric intake after 2 days of high-fat feeding, body weights of A/J mice remained stable. On and after 1 wk of high-fat feeding, A/J mice adjusted their food intake to consume the same amount of calories as mice fed a low-fat diet; thus their body weight and insulin, corticosterone, free fatty acid, and glucose levels remained unchanged for 4 wk. We found no changes in hypothalamic expression of several orexigenic and/or anorexigenic neuropeptides known to play an important role in energy homeostasis for the duration of the study. Uncoupling protein-2 mRNA expression in brown adipose tissue, however, was significantly upregulated after 2 days of high-fat feeding and tended to remain elevated for the duration of the 4-wk study. Gene array analysis revealed that several genes are up- or downregulated in response to 2 days and 1 wk of high-fat feeding. Real-time PCR analysis confirmed that expression of the hypothalamic IL-1 pathway (IL-1beta, IL-1 type 1 and 2 receptors, and PPM1b/PP2C-beta, a molecule that has been implicated in the inhibition of transforming growth factor-beta-activated kinase-1-mediated IL-1 action) is altered after 2 days, but not 1 wk, of high-fat feeding. The role of additional molecules discovered by microarray analysis needs to be further explored in the future.

Lack of stearoyl-CoA desaturase 1 upregulates basal thermogenesis but causes hypothermia in a cold environment

Stearoyl-CoA desaturase (SCD) is a microsomal enzyme involved in the biosynthesis of oleate and palmitoleate. Mice with a targeted disruption of the SCD1 isoform (SCD1-/-) exhibit reduced adiposity and increased energy expenditure. To address whether the energy expenditure is attributable to increased thermogenesis, we investigated the effect of SCD1 deficiency on basal and cold-induced thermogenesis. SCD1-/- mice have increased expression of uncoupling proteins in brown adipose tissue (BAT) relative to controls. The beta3-adrenergic receptor (beta3-AR) expression was increased and the phosphorylation of cAMP response element binding protein and the protein level of peroxisome proliferator-activated receptor-gamma coactivator-1alpha were increased in the SCD1-/- mice. Both lipolysis and fatty acid oxidation were increased in the SCD1-/- mice. When exposed to 4 degrees C, SCD1-/- mice showed hypothermia, hypoglycemia, and depleted liver glycogen. High levels of dietary oleate partially compensated for the hypothermia and rescued plasma glucose and liver glycogen. These results suggest that SCD1 deficiency stimulates basal thermogenesis through the upregulation of the beta3-AR-mediated pathway and a subsequent increase in lipolysis and fatty acid oxidation in BAT. The hypothermia and hypoglycemia in cold-exposed SCD1-/- mice and the compensatory recovery by oleate indicate an important role of SCD1 gene expression in thermoregulation.

Activation of the sympathetic nervous system by galanin-like peptide--a possible link between leptin and metabolism.

The effects of leptin upon body weight (BW) cannot be explained by its anorectic actions alone. Part of the metabolic changes elicited by leptin includes sympathetic nervous system activation leading to increased energy expenditure. Galanin-like peptide (GALP), a recently described hypothalamic neuropeptide, is up-regulated by leptin and has anorectic effects in the mouse. We postulated that GALP mediates effects of leptin upon metabolism. To test this hypothesis, we administered GALP centrally to the leptin-deficient ob/ob mouse. Acutely, GALP induced a decrease in food intake and BW, both of which remained significant relative to controls for 4 d. Chronic GALP administration resulted in a sustained decrease in BW and an increase in core body temperature, despite significant recovery of food intake. In a pair-fed model, chronic GALP treatment resulted in a greater decrease in BW than that seen in controls. Furthermore, GALP treatment resulted in increased body temperature and uncoupling protein 1 mRNA and protein in brown adipose tissue compared with controls. The expression of pro-opiomelanocortin (POMC) mRNA in the arcuate nucleus was decreased after chronic GALP treatment. These observations suggest that leptin's activation of the sympathetic nervous system, and ultimately thermogenesis, may be partially mediated by GALP through a melanocortin-independent mechanism.

Resolution and identification of Gq/G11alpha and Gialpha/Goalpha proteins in brown adipose tissue: effect of cold acclimation.

Levels of guanine nucleotide-binding proteins G(q)alpha and G(11)alpha, which produce receptor regulation of phospholipase C, were measured immunologically in purified plasma membrane fractions of hamster brown adipose tissue (BAT). This was achieved by immunoblotting with antisera (CQ series) that identify these two polypeptides equally, following separation of the plasma membranes using SDS-PAGE in the presence of 6 M urea, i.e. conditions that can resolve G(q)alpha and G(11)alpha. The ratio of levels of G(q)alpha to G(11)alpha was 1:1. A similar approach was used for resolution and identification of G(o)1alpha and G(o)2alpha, the latter representing the prevailing form of G(o)alpha proteins in this tissue. Although clearly recognized in brain microsomes, which were used as positive controls, no detected levels of G(o)*alpha protein were noted. Using specific anti-peptide antibodies directed against the carboxy-terminal decapeptide of G(i)3alpha, this G protein was also found to be expressed in BAT tissue. Cold acclimation resulted in reduction of the plasma membrane levels of all these Galpha proteins.

Effects of Intravenously Infused Leptin on Insulin Sensitivity and on the Expression of Uncoupling Proteins in Brown Adipose Tissue

Effects of Intravenously Infused Leptin on Insulin Sensitivity and on the Expression of Uncoupling Proteins in Brown Adipose Tissue

Effects of intravenously infused leptin on insulin sensitivity and on the expression of uncoupling proteins in brown adipose tissue.

Centrally administered leptin has been shown to increase insulin-stimulated glucose utilization and to favor the expression of uncoupling proteins (UCPs). To study if leptin also has direct peripherally mediated effects on these processes, this hormone (1 mg/day) or its vehicle was infused i.v. for 4 days to lean rats and insulin-stimulated glucose utilization in skeletal muscle and adipose tissue as well as the expression of UCP messenger RNAs (mRNAs) in brown adipose tissue were measured. I.v. leptin administration resulted in decreases in food intake (31%), body weight gain, and plasma insulin levels (45%), in increases in overall (23%) as well as brown adipose tissue and muscle glucose utilization, and in decreases in white adipose tissue glucose uptake. Most of these changes were mimicked, in control rats, by giving them the same amount of food as that consumed by the leptin-infused group (pair-feeding). I.v. leptin infusion also favored the expression of UCPs in brown adipose tissue, either by increasing their expression or preventing the fall occurring during the pair-feeding regimen. Relative UCP expression levels were 100, 104, and 33 for UCP1, 100, 191, and 125 for UCP2 and 100, 107, and 29 for UCP3 in ad libitum fed control rats, in leptin-treated rats and in pair-fed control rats, respectively. These results suggest that the overall effect of leptin on glucose utilization and on the expression of UCPs may be mediated through central mechanism.

Fish (Bonito) Oil Supplementation Enhances the Expression of Uncoupling Protein in Brown Adipose Tissue of Rat

ADVERTISEMENT RETURN TO ISSUECommunicationNEXTFish (Bonito) Oil Supplementation Enhances the Expression of Uncoupling Protein in Brown Adipose Tissue of RatTeruo Kawada, Shun Kayahashi, Yoshifumi Hida, Ken-ji Koga, Yoshitaka Nadachi, and Tohru FushikiView Author Information Laboratory of Nutrition Chemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-01, Japan, and Research and Development Division, JANIFTEC, Inc., Chuoh-ku, Tokyo 104, JapanCite this: J. Agric. Food Chem. 1998, 46, 4, 1225–1227Publication Date (Web):March 14, 1998Publication History Received29 December 1997Published online14 March 1998Published inissue 1 April 1998https://doi.org/10.1021/jf9711000Copyright © 1998 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views373Altmetric-Citations31LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (47 KB) Get e-AlertsSUBJECTS:Animal derived food,Energy,Lipids,Redox reactions,Rodent models Get e-Alerts

Progress in Understanding the Genetics of Obesity

Progress in understanding the genetics of obesity has moved rapidly in the past few years. The genes for all of the single gene defects that produce obesity in experimental animals have now been cloned. The new insights from these models are one spur for the examination of possible links to human obesity. In thinking about the biology of obesity produced by single gene defects, it must be kept in mind that adrenalectomy can prevent the phenotypic expression in all of the single gene models of obesity. Thus, nongenetic components can play a major role in regulating even single gene models of obesity. Transgenic mice have also expanded our understanding of obesity. Transgenic models that both increase and decrease body fat have been published. Of particular interest from the perspective of the physiological control of obesity is the destruction of the uncoupling protein in brown adipose tissue, which is followed by hyperphagia and obesity, suggesting that the sympathetic nervous system is involved in both modulation of food intake and energy storage. Gene mapping using quantitative trait loci and studies of candidate genes have been applied to experimental models of animals with differing susceptibilities to dietary fat and have been applied to the human genome in more detail.

Nonshivering thermogenesis in adult and aged C57BL/6J mice housed at 22 degrees C and at 29 degrees C.

Twelve- and 28-month-old C57BL/6J male mice were housed either at room temperature of 22 degrees C or at thermoneutrality (29 degrees C) during the two months prior to experiments. Acute experiments were conducted under anesthesia, myorelaxation, and artificial ventilation. We recorded efferent electrical impulse activity in one of the sympathetic nerves innervating the interscapular brown adipose tissue in response to acute cold stimulation, when body temperature was lowered 7.5 degrees C below control level. In separate experiments we measured O2 consumption and CO2 production and calculated the nonshivering thermogenesis. We also measured the concentration of uncoupling protein in interscapular brown adipose tissue before and after three-hour cold stress. In aged mice, both sympathetic nervous activity and nonshivering thermogenesis were lower in animals housed at thermoneutrality (29 degrees C) than in mice housed at 22 degrees. Among mice maintained at 22 degrees C, but not at thermoneutrality, aged animals had greater nonshivering thermogenesis and greater cold induced concentration of uncoupling protein in the brown adipose tissue than adults. Sympathetic nervous outflow to brown adipose tissue was always greater in aged mice, regardless of the temperature of acclimation. We concluded that aged mice, housed at 22 degrees C, showed the changes in nonshivering thermogenesis associated with cold acclimation. However, an increased sympathetic outflow to brown adipose tissue in aged animals reflects an age-related elevation of the tone and responsiveness of the sympathetic nervous system.

Cold-Induced Heat Shock Protein Expression in Rat Aorta and Brown Adipose Tissue

Recent reports indicate that Heat Shock Proteins (HSPs) are induced in mammalian tissues as part of a homeostatic response to environmental stressors. Administration of sympathomimetic drugs and neuroendocrine stress hormones has been shown to evoke an HSP response in unstressed animals indicating that cell signaling events exists that couple specific neurotransmitter/hormone-receptor interactions with HSP expression in mammalian tissues. Herein, we demonstrate that exposure of rats to a cold ambient temperature (6°C) results in increased expression of constitutive and inducible members of the HSP70 gene family in association with increased expression of the mitochondrial uncoupling protein in brown adipose tissue (BAT). Increased HSP70 expression was not restricted to BAT because HSP70 was also induced in the aorta. This cold-induced HSP response is characterized by a transient increase in HSP70 protein and mRNA in both tissues during continued exposure. Ganglionic blockade prevented cold-induced HSP70 expression in BAT and aorta, indicating that sympathetic activity is requisite to this response. Administration of the α1-adrenergic receptor antagonist, prazosin, also blocked expression, further delineating possible signaling mechanisms mediating this response. Apparently, cells in some mammalian tissues have adopted unique cellular regulatory mechanisms to support HSP induction that have been incorporated into the physiological response of the entire organism to an environmental stressor.

Induction of uncoupling protein in brown adipose tissue: Synergy between norepinephrine and pioglitazone, an insulin-sensitizing agent

Insulin resistance and obesity in rodent models of non-insulin-dependent diabetes mellitus have been correlated with ablated or defective brown adipose tissue (BAT) function. The mitochondrial uncoupling protein (UCP) allows BAT to perform its unique role in facultative energy expenditure. In this study, we observed an increase in both BAT mass and the expression of UCP mRNA in BAT from obese diabetic mice and their lean littermates following treatment with the thiazolidinedione pioglitazone, a novel insulin-sensitizing agent. Thus, we wanted to ascertain if pioglitazone directly induces BAT differentiation. We found that treatment for 48 hr with pioglitazone caused a 32-fold increase in UCP mRNA, whereas a 7-hr treatment with norepinephrine caused a 24-fold increase in expression. Cells treated with pioglitazone for 48 hr, with norepinephrine added during the last 7 hr, demonstrated a 59-fold increase in UCP mRNA. However, simultaneous treatment with pioglitazone and repeated treatment norepinephrine for 48 hr yielded a greater than 200-fold increase in UCP mRNA. Examination of UCP protein levels demonstrated a similar time-dependent increase with pioglitazone and/or norepinephrine treatment, as well as a synergistic increase with concurrent pioglitazone and norepinephrine treatment. This study shows that pioglitazone exerts a direct effect on BAT cells in vitro by increasing UCP mRNA and protein levels, and that it also synergizes with norepinephrine perhaps by inducing and stabilizing UCP mRNA and/or preventing proteolysis of UCP protein.

Uncoupling protein in brown adipose tissue: molecular differentiation of the adipose tissues.

Uncoupling protein in brown adipose tissue: molecular differentiation of the adipose tissues.