Regulation of adipose triglyceride lipase by rosiglitazone

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.

Liu, L.-F.
Purushotham, A.
Wendel, A. A.
Koba, K.
DeIuliis, J.
Lee, K.
Belury, M. A.
Item Type: 
Journal Article
Publication Title: 
Diabetes, Obesity & Metabolism
Journal Abbreviation: 
Diabetes Obes Metab
Publication Date: 
Feb 2009
Publication Year: 
Library Catalog: 
NCBI Published Medical (?)
PMID: 18643838 PMCID: PMC3814028

Turabian/Chicago Citation

L.-F. Liu, A. Purushotham, A. A. Wendel, K. Koba, J. DeIuliis, K. Lee and M. A. Belury. Feb 2009. "Regulation of adipose triglyceride lipase by rosiglitazone." Diabetes, Obesity & Metabolism 11: 2: 131-142. 10.1111/j.1463-1326.2008.00916.x.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1111/j.1463-1326.2008.00916.x | issn = 1463-1326 | volume = 11 | pages = 131-142 | last = Liu | first = L.-F. | coauthors = Purushotham, A., Wendel, A. A., Koba, K., DeIuliis, J., Lee, K., Belury, M. A. | title = Regulation of adipose triglyceride lipase by rosiglitazone | journal = Diabetes, Obesity & Metabolism | date = Feb 2009 | pmid = | pmc = }} </ref>