Depot-specific effects of the PPARγ agonist rosiglitazone on adipose tissue glucose uptake and metabolism
Depot-specific effects of the PPARγ agonist rosiglitazone on adipose tissue glucose uptake and metabolism
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DOI：
10.1194/jlr.m800620-jlr200
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发表时间：
2009-06-01
影响因子：
6.5
通讯作者：
Deshaies, Yves
中科院分区：
文献类型：
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作者：
Festuccia, William T.;Blanchard, Pierre-Gilles;Deshaies, Yves
我们通过研究PPAR激活对VF和SF的葡萄糖摄取和代谢、脂肪生成和参与三酰甘油（TAG）合成的酶的影响，研究了过氧化物酶体增殖物激活受体γ (PPAR γ)激动作用将脂肪从内脏（VF）重新分配到皮下脂肪（SF）的机制。用罗格列酮（15mg /kg/天）治疗或不治疗7 d的大鼠，在体内评估其腹膜后VF和腹股沟SF的葡萄糖摄取和脂肪生成情况，在体外评估其葡萄糖代谢、基因表达和甘油磷酸酰基转移酶（GPAT）、磷脂磷酸酶-1（或脂素-1）和二酰基甘油酰基转移酶的活性。罗格列酮增加SF葡萄糖摄取、GLUT4 mRNA和胰岛素刺激的葡萄糖氧化、转化为乳酸、糖原、甘油和脂肪酸成分。在VF中，罗格列酮只刺激葡萄糖与tag -甘油的结合，比SF低（1.5倍对3倍）。罗格列酮显著上调SF中参与糖酵解、克雷布斯循环、糖原合成和脂肪生成的蛋白质mRNA水平，而在VF中则较低。罗格列酮在SF中比在VF中更强烈地激活tag -甘油合成（2.8倍比1.9倍）和脂质活性（4.6倍比1.5倍），而GPAT活性在两个仓库中相似地增加。SF中葡萄糖摄取和细胞内代谢的优先增加有助于PPAR γ介导的TAG从VF到SF的再分配，这反过来有利于全局胰岛素增敏。-费斯塔西亚，w.t., p.g.布兰查德，V. Turcotte， M. Laplante， M. Sariahmetoglu， D. N. Brindley和Y. Deshaies。PPARg激动剂罗格列酮对脂肪组织葡萄糖摄取和代谢的仓库特异性影响。[j] .油脂杂志。2009。: 1185 - 1194。
We investigated mechanisms whereby peroxisome proliferator-activated receptor gamma (PPAR gamma) agonism redistributes lipid from visceral (VF) toward subcutaneous fat (SF) by studying the impact of PPARg 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 PPAR gamma-mediated redistribution of TAG from VF to SF, which in turn favors global insulin sensitization.-Festuccia, W. T., P-G. Blanchard, V. Turcotte, M. Laplante, M. Sariahmetoglu, D. N. Brindley, and Y. Deshaies. Depot-specific effects of the PPARg agonist rosiglitazone on adipose tissue glucose uptake and metabolism. J. Lipid Res. 2009. 50: 1185-1194.