4.7 Article

Regulation of adipose triglyceride lipase by rosiglitazone

Journal

DIABETES OBESITY & METABOLISM
Volume 11, Issue 2, Pages 131-142

Publisher

WILEY
DOI: 10.1111/j.1463-1326.2008.00916.x

Keywords

adipocyte; ATGL; PPAR gamma; rosiglitazone

Funding

  1. National Institutes of Health [5R21AT003520-02)]
  2. Ohio Agriculture Research and Development Center (OARDC)
  3. Hazel Williams Lapp Fellowship

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To elucidate the mechanism by which rosiglitazone regulates adipose triglyceride lipase (ATGL). Male C57Bl/6 mice were treated with rosiglitazone daily (10 mg/kg body weight), and adipose tissues were weighed and preserved for mRNA and protein analysis of ATGL. In parallel, preadipocyte (3T3-L1) cells were differentiated with insulin/dexamethasone/3-isobutyl-1-methlxanthine cocktail or rosiglitazone, and ATGL levels were measured with real-time PCR, western blotting and immunohistochemistry. Rosiglitazone concomitantly promoted differentiation of pre-adipocytes to functional adipocytes and induced mRNA levels of ATGL. The peroxisome proliferator-activated receptor-gamma (PPAR gamma) antagonist bisphenol A diglycidyl ether significantly abrogated the induction of mRNA, but not protein levels of ATGL by rosiglitazone in differentiated 3T3-L1 adipocytes. In the presence of epinephrine rosiglitazone stimulated free fatty acid release and increased diacylglycerol acyltransferase-1 (DGAT-1) mRNA suggest that ATGL and DGAT-1 may be cooperatively involved in rosiglitazone-stimulated triglyceride hydrolysis and fatty acid re-esterification in 3T3-L1 adipocytes. Treatment of 3T3-L1 adipocytes with rosiglitazone or insulin did not appear to alter localization of ATGL staining surrounding lipid droplets. Finally, we found that rosiglitazone increased ATGL mRNA levels in 3T3-L1 adipocytes in the presence of cycloheximide, an inhibitor of protein synthesis, suggesting that rosiglitazone regulation of ATGL occurs at the transcriptional level. Rosiglitazone directly regulates transcription of ATGL, likely through a PPAR gamma-mediated mechanism.

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