Research Article
Depot-specific effects of the PPARγ agonist rosiglitazone on adipose tissue glucose uptake and metabolism[S]

https://doi.org/10.1194/jlr.M800620-JLR200Get rights and content
Under a Creative Commons license
open access

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.

glucose oxidation
lipogenesis
glycerol 3-phosphate acyltransferase
lipin
diacylglycerol acyltransferase
visceral fat
subcutaneous fat

Cited by (0)

Abbreviations

  1. CIDEC, cell death-inducing DNA fragmentation factor-α-like effector

  2. DGAT, diacylglycerol acyltransferase

  3. G6PDH, glucose 6-phosphate dehydrogenase

  4. GLUT, glucose transporter

  5. GPAT, glycerol 3-phosphate acyltransferase

  6. GyS2, glycogen synthase 2

  7. ME, malic enzyme

  8. NEFA, nonesterified fatty acid

  9. PAP-1, phosphatidate phosphatase-1

  10. PEPCK, phosphoenolpyruvate carboxykinase

  11. PPARγ, peroxisome proliferator-activated receptor γ

  12. SF, subcutaneous fat

  13. SREBP1, sterol regulatory binding protein 1

  14. TAG, triacylglycerol

  15. UDPG-PPL, UDP-glucose pyrophosphorylase

  16. VF, visceral fat

  17. WAT, white adipose tissue

This work was supported by a grant from the Canadian Institutes of Health Research to Y.D. and from the Heart and Stroke Foundation of Canada to D.N.B. P-G.B. was the recipient of a Frederick Banting and Charles Best Canada Graduate Scholarships, Doctoral Award from the Canadian Institutes of Health Research.

Published, JLR Papers in Press, February 5, 2009.

[S]

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of one figure and one table.