| 18643838 |
Liu LF, Purushotham A, Wendel AA, Koba K, DeIuliis J, Lee K, Belury MA: Regulation of adipose triglyceride lipase by rosiglitazone. . Diabetes Obes Metab. 2009 Feb;11(2):131-42. Epub 2008 Jul 17.
AIM: To elucidate the mechanism by which rosiglitazone regulates adipose triglyceride lipase (ATGL). METHODS: 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. RESULTS: Rosiglitazone concomitantly promoted differentiation of pre-adipocytes to functional adipocytes and induced mRNA levels of ATGL. The peroxisome proliferator-activated receptor-gamma (PPARgamma) 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. CONCLUSIONS: Rosiglitazone directly regulates transcription of ATGL, likely through a PPARgamma-mediated mechanism. |
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