title: The modulation of adiponectin by STAT5-activating hormones.
abstract: Adiponectin is a hormone secreted from adipocytes that plays an important role in insulin sensitivity and protects against metabolic syndrome. Growth hormone (GH) and prolactin (PRL) are potent STAT5 activators that regulate the expression of several genes in adipocytes. Studies have shown that the secretion of adiponectin from adipose tissue is decreased by treatment with PRL and GH. In this study, we demonstrate that 3T3-L1 adipocytes treated with GH or PRL exhibit a reduction in adiponectin protein levels. Furthermore, we identified three putative STAT5 binding sites in the murine adiponectin promoter and show that only one of these, located at -3,809, binds nuclear protein in a GH- or PRL-dependent manner. Mutation of the STAT5 binding site reduced PRL-dependent protein binding, and supershift analysis revealed that STAT5A and -5B, but not STAT1 and -3, bind to this site in response to PRL. Chromatin immunoprecipitation (IP) analysis demonstrated that only STAT5A, and not STAT1 and -3, bind to the murine adiponectin promoter in a GH-dependent manner in vivo. Adiponectin promoter/reporter constructs were responsive to GH, and chromatin IP analysis reveals that STAT5 binds the adiponectin promoter in vivo following GH stimulation. Overall, these data strongly suggest that STAT5 activators regulate adiponectin transcription through the binding of STAT5 to the -3,809 site that leads to decreased adiponectin expression and secretion. These mechanistic observations are highly consistent with studies in mice and humans that have high GH or PRL levels that are accompanied by lower circulating levels of adiponectin.
authors.affiliation: Adipocyte Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana; and.
authors.forename: Ursula A
authors.initials: UA
authors.lastname: White
authors.affiliation: Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana.
authors.forename: Joel
authors.initials: J
authors.lastname: Maier
authors.affiliation: Adipocyte Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana; and Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Adipocyte Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana; and.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Richard
authors.affiliation: Adipocyte Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana; and Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana jsteph1@lsu.edu.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Stephens
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D013006:Growth Hormone / Q000494:pharmacology*; D051379:Mice; D011388:Prolactin / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D050799:STAT5 Transcription Factor / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D050799:STAT5 Transcription Factor; D011388:Prolactin; D013006:Growth Hormone
keywords: signal transducer and activator of transcription 5