Depot-specific effects of the PPARgamma agonist rosiglitazone on adipose tissue glucose uptake and metabolism.
We investigated mechanisms whereby peroxisome proliferator-activated receptor gamma (PPARgamma) agonism redistributes lipid from visceral (VF) toward subcutaneous fat (SF) by studying the impact of PPARgamma 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 PPARgamma-mediated redistribution of TAG from VF to SF, which in turn favors global insulin sensitization.
Festuccia
William T
WT
Laval Hospital Research Center and Department of Anatomy and Physiology, Faculty of Medicine, Laval University, Quebec, Canada G1V 4G5.
Blanchard
Pierre-Gilles
PG
Turcotte
Véronique
V
Laplante
Mathieu
M
Sariahmetoglu
Meltem
M
Brindley
David N
DN
Deshaies
Yves
Y
D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects; D008297:Male; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists*; D010711:Phosphatidate Phosphatase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D050151:Subcutaneous Fat / Q000187:drug effects / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D014280:Triglycerides / Q000096:biosynthesis
D051275:Glucose Transporter Type 4; D007328:Insulin; C530902:Lpin1 protein, rat; D009687:Nuclear Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D005992:Glycerol-3-Phosphate O-Acyltransferase; D010711:Phosphatidate Phosphatase; D005947:Glucose