STAT5 activators modulate acyl CoA oxidase (AOX) expression in adipocytes and STAT5A binds to the AOX promoter in vitro.
Growth hormone (GH) diminishes adipose tissue mass in vivo and prolactin (PRL) can also modulate adipocyte metabolism. Both GH and PRL are potent activators of STAT5 and exert a variety of effects on adipocyte gene expression. In this study, we have demonstrated that GH and PRL increase the mRNA of acyl CoA oxidase in 3T3-L1 adipocytes. We also identified seven putative STAT elements in the murine AOX promoter. We observed that GH modulates protein binding to the majority of these promoter elements. However, GH induced very potent binding to -1841 to -1825 of the murine AOX promoter. EMSA supershift analysis revealed that this site was specifically bound by STAT5A, but not by STAT1 or STAT3. Taken together, these data strongly suggest that GH directly induces the expression of AOX in adipocytes through STAT5A binding to the -1841 to -1825 site within the AOX promoter. Our observations are consistent with other studies that demonstrate that STAT5 activators modulate fatty acid oxidation.
Coulter
Ann A
AA
Department of Biological Sciences, Louisiana State University, 202 Life Sciences Bldg., Baton Rouge, LA 70803, USA.
Stephens
Jacqueline M
JM
D041721:3T3-L1 Cells; D042962:Acyl-CoA Oxidase / Q000235:genetics*; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D013006:Growth Hormone / Q000494:pharmacology*; D051379:Mice; D011388:Prolactin / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020218:Response Elements; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism*
D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; C494093:Stat5a protein, mouse; D011388:Prolactin; D013006:Growth Hormone; D042962:Acyl-CoA Oxidase