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  • 标题:Depot-specific effects of the PPARγ agonist rosiglitazone on adipose tissue glucose uptake and metabolism
  • 本地全文:下载
  • 作者:William T. Festuccia ; Pierre-Gilles Blanchard ; Véronique Turcotte
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2009
  • 卷号:50
  • 期号:6
  • 页码:1185-1194
  • DOI:10.1194/jlr.M800620-JLR200
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:We investigated mechanisms whereby peroxisome proliferator-activated receptor γ (PPARγ) agonism redistributes lipid from visceral (VF) toward subcutaneous fat (SF) by studying the impact of PPARγ activation on VF and SF glucose uptake and metabolism, lipogenesis, and enzymes involved in triacylglycerol (TAG) synthesis. VF (retroperitoneal) and SF (inguinal) of rats treated or not for 7 days with rosiglitazone (15 mg/kg/day) were evaluated in vivo for glucose uptake and lipogenesis and in vitro for glucose metabolism, gene expression, and activities of glycerolphosphate acyltransferase (GPAT), phosphatidate phosphatase-1 (or lipin-1), and diacylglycerol acyltransferase. Rosiglitazone increased SF glucose uptake, GLUT4 mRNA, and insulin-stimulated glucose oxidation, conversion to lactate, glycogen, and the glycerol and fatty acid components of TAG. In VF, only glucose incorporation into TAG-glycerol was stimulated by rosiglitazone and less so than in SF (1.5- vs. 3-fold). mRNA levels of proteins involved in glycolysis, Krebs cycle, glycogen synthesis, and lipogenesis were markedly upregulated by rosiglitazone in SF and again less so in VF. Rosiglitazone activated TAG-glycerol synthesis in vivo (2.8- vs. 1.9-fold) and lipin activity (4.6- vs. 1.5-fold) more strongly in SF than VF, whereas GPAT activity was increased similarly in both depots. The preferential increase in glucose uptake and intracellular metabolism in SF contributes to the PPARγ-mediated redistribution of TAG from VF to SF, which in turn favors global insulin sensitization.
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