The regulation of fatty acid synthase by STAT5A.
Growth hormone (GH) diminishes adipose tissue mass in vivo and decreases expression and activity of fatty acid synthase (FAS) in adipocytes. GH and prolactin (PRL) are potent activators of STAT5 and exert adipogenic and antiadipogenic effects in adipocytes. In this study, we demonstrate that GH and PRL decrease the mRNA and protein levels of FAS in 3T3-L1 adipocytes. We present evidence that indicates that FAS is repressed at the level of transcription. In addition, PRL responsiveness was shown to exist between -1,594 and -700 of the rat FAS promoter. Moreover, responsiveness to PRL was abolished with mutation of a site at position -908 to -893, which we have shown to bind STAT5A in a PRL-dependent manner. Taken together, these data strongly suggest that PRL directly represses expression of FAS in adipocytes through STAT5A binding to the -908 to -893 site. Furthermore, our results indicate that STAT5A has an antilipogenic function in adipocytes and may contribute to the regulation of energy balance.
Louisiana State University, Department of Biological Sciences, 202 Life Sciences Bldg., Baton Rouge, LA 70803, USA.
Jessica C
JC
Hogan
Jacqueline M
JM
Stephens
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D064429:Fatty Acid Synthases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017930:Genes, Reporter; D013006:Growth Hormone / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008894:Milk Proteins / Q000378:metabolism*; D011388:Prolactin / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; C494094:Stat5a protein, rat; D015534:Trans-Activators; D011388:Prolactin; D013006:Growth Hormone; D008156:Luciferases; D064429:Fatty Acid Synthases