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Regulation of adipose triglyceride lipase by rosiglitazone
Author(s) -
Liu L.F.,
Purushotham A.,
Wendel A. A.,
Koba K.,
DeIuliis J.,
Lee K,
Belury M. A.
Publication year - 2009
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2008.00916.x
Subject(s) - rosiglitazone , adipose triglyceride lipase , medicine , endocrinology , chemistry , lipid droplet , adipose tissue , perilipin , 3t3 l1 , adipogenesis , triglyceride , adipocyte , lipolysis , insulin , biology , cholesterol
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‐γ (PPARγ) 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 PPARγ‐mediated mechanism.