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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brown adipose and muscle tissues can increase energy expenditure via adaptive thermogenesis, thereby protecting against obesity. Mouse peroxisome proliferator activated receptor gamma coactivator 1 (Pgc1) has been reported to enhance the expression of uncoupling protein-1, a key mediator of thermogenesis in brown adipose tissue (Puigserver et al., 1998, Cell 92, 829-839). We report here the characterization of the human PPARGC1 gene. PPARGC1 spans a genomic region of approximately 67 kb, is composed of 13 exons, and encodes a 91-kDa protein that exhibits 94% amino acid identity with the mouse ortholog. mRNA species, transcribed from the TATA-less promoter, are 6.4 and 5.3 kb in length due to utilization of two polyadenylation signals. Northern blotting revealed expression of both transcripts in heart, skeletal muscle, and kidney and to a lesser extent in liver, brain, and pancreas as well as in the perirenal adipose tissue of a pheochromocytoma patient. PPARGC1 was mapped to chromosome 4p15.1, a region that has been associated with basal insulin levels in Pima Indians. Hence, PPARGC1 expression might influence insulin sensitivity as well as energy expenditure, thereby contributing to the development and pathophysiology of human obesity.
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PMID:Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression. 1058 75

Type 2 diabetes mellitus is a complex metabolic disease that occurs when insulin secretion can no longer compensate insulin resistance in peripheral tissues. At the molecular level, insulin resistance correlates with impaired insulin signalling. This review provides new insights into the molecular mechanisms of insulin action and resistance in brown adipose tissue and pinpoints the role of this tissue in the control of glucose homeostasis. Brown adipocytes are target cells for insulin and IGF-I action, especially during late foetal development when insulin supports survival and promotes both adipogenic and thermogenic differentiation. The main pathway involved in insulin induction of adipogenic differentiation, monitored by fatty acid synthase expression, is the cascade insulin receptor substrate (IRS)-1/phosphatidylinositol 3-kinase (PI3K)/Akt. Glucose transport in these cells is maintained mainly by the activity of GLUT4. Acute insulin treatment stimulates glucose transport largely by mediating translocation of GLUT4 to the plasma membrane, involving the activation of IRS-2/PI3K, and the downstream targets Akt and protein kinase C zeta. Tumour necrosis factor (TNF-alpha) caused insulin resistance on glucose uptake by impairing insulin signalling at the level of IRS-2. Activation of stress kinases and phosphatases by this cytokine contribute to insulin resistance. Furthermore, brown adipocytes are also target cells for rosiglitazone action since they show a high expression of peroxisome proliferator activated receptor gamma, and rosiglitazone increased the expression of the thermogenic uncoupling protein 1. Rosiglitazone ameliorates insulin resistance provoked by TNF-alpha, completely restoring insulin-stimulated glucose uptake in parallel to the insulin signalling cascade. Accordingly, foetal brown adipocytes represent a model for investigating insulin action, as well as for the mechanism by which rosiglitazone increase insulin sensitivity under situations that mimic insulin resistance.
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PMID:The brown adipose cell: a model for understanding the molecular mechanisms of insulin resistance. 1565 20

Telmisartan is an angiotensin receptor blocker (ARB) and a selective peroxisome proliferator activated receptor gamma (PPARG) modulator. Recently, we tested metabolic effects of telmisartan (5 mg/kg body weight) in spontaneously hypertensive rats (SHR) fed a diet containing 60 % fructose, a widely used model of the metabolic syndrome. Surprisingly, we observed acute toxic effects of telmisartan. Rats lost body weight rapidly and died within 2 to 3 weeks due to bleeding into the upper gastrointestinal tract. SHR fed a high fructose diet and treated with telmisartan exhibited rapid decrease in blood pressure when compared to the SHR fed a high fructose diet and treated with valsartan. Concentrations of both unconjugated telmisartan and telmisartan glucuronide in the liver of SHR rats fed a high fructose diet were approximately 4 fold higher when compared to Brown Norway (BN) rats fed the same diet. Plasma concentrations of unconjugated telmisartan in the SHR were about 5 fold higher when compared to BN rats while plasma levels of telmisartan glucuronide were similar between the strains. Testing of other rat strains, diets, and the ARB valsartan showed that toxic effects of telmisartan in combination with high fructose diet are specific for the SHR. These results are consistent with the possibility that in some circumstances, SHR are predisposed to telmisartan toxicity possibly because of a genetically determined disturbance in telmisartan metabolism.
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PMID:Acute toxic effects of telmisartan in spontaneously hypertensive rats fed a high fructose diet. 3020 69

The mechanisms underlying glucocorticoid (GC)-increased adiposity are poorly understood. Brown adipose tissue (BAT) acquires white adipose tissue (WAT) cell features defined as BAT whitening under certain circumstances. The aim of our current study was to investigate the possibility and mechanisms of GC-induced BAT whitening. Here, we showed that one-week dexamethasone (Dex) treatment induced BAT whitening, characterized by lipid droplet accumulation, in vitro and in vivo. Furthermore, autophagy and ATG7 (autophagy related 7) expression was induced in BAT by Dex, and treatment with the autophagy inhibitor chloroquine or adenovirus-mediated ATG7 knockdown prevented Dex-induced BAT whitening and fat mass gain. Moreover, Dex-increased ATG7 expression and autophagy was mediated by enhanced expression of BTG1 (B cell translocation gene 1, anti-proliferative) that stimulated activity of CREB1 (cAMP response element binding protein 1). The importance of BTG1 in this regulation was further demonstrated by the observed BAT whitening in adipocyte-specific BTG1-overexpressing mice and the attenuated Dex-induced BAT whitening and fat mass gain in mice with BTG1 knockdown in BAT. Taken together, we showed that Dex induces a significant whitening of BAT via BTG1- and ATG7-dependent autophagy, which might contribute to Dex-increased adiposity. These results provide new insights into the mechanisms underlying GC-increased adiposity and possible strategy for preventing GC-induced side effects via the combined use of an autophagy inhibitor.Abbreviations: ACADL: acyl-Coenzyme A dehydrogenase, long-chain; ACADM: acyl-Coenzyme A dehydrogenase, medium-chain; ACADS: acyl-Coenzyme A dehydrogenase, short-chain; ADIPOQ: adiponectin; AGT: angiotensinogen; Atg: autophagy-related; BAT: brown adipose tissue; BTG1: B cell translocation gene 1, anti-proliferative; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; CIDEA: cell death-inducing DNA fragmentation factor, alpha subunit-like effector A; CPT1B: carnitine palmitoyltransferase 1b, muscle; CPT2: carnitine palmitoyltransferase 2; CQ: chloroquine; Dex: dexamethasone; eWAT: epididymal white adipose tissue; FABP4: fatty acid binding protein 4, adipocyte; FFAs: free fatty acids; GCs: glucocorticoids; NRIP1: nuclear receptor interacting protein 1; OCR: oxygen consumption rate; PBS: phosphate-buffered saline; PPARA: peroxisome proliferator activated receptor alpha; PPARG: peroxisome proliferator activated receptor gamma; PPARGC1A: peroxisome proliferator activated receptor, gamma, coactivator 1 alpha; PRDM16: PR domain containing 16; PSAT1: phosphoserine aminotransferase 1; RB1: RB transcriptional corepressor 1; RBL1/p107: RB transcriptional corepressor like 1; SQSTM1: sequestosome 1; sWAT: subcutaneous white adipose tissue; TG: triglycerides; UCP1: uncoupling protein 1 (mitochondrial, proton carrier); WT: wild-type.
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PMID:Autophagy inhibition prevents glucocorticoid-increased adiposity via suppressing BAT whitening. 3118 63