title: Critical roles of the p160 transcriptional coactivators p/CIP and SRC-1 in energy balance.
abstract: Several transcriptional coactivators have been implicated in modulating the transcriptional activities of nuclear hormone receptors in vitro. Potential roles of these cofactors in important physiological processes such as energy homeostasis remain unknown. We report here that a developmental arrest in interscapular brown fat and defective adaptive thermogenesis occur in mice lacking both the p160 family transcriptional coactivators SRC-1 and p/CIP due to a failure in induction of selective PPARgamma target genes involved in adipogenesis and mitochondrial uncoupling. In the absence of p/CIP and SRC-1, mice eat more food on both regular chow and a high-fat diet because of decreased blood leptin levels. However, the p/CIP(-/-)/SRC-1(-/-) mice are lean and resistant to high-fat-diet-induced obesity. They exhibit increased basal metabolic rates and heightened levels of physical activity. Therefore, p/CIP and SRC-1 play critical roles in energy balance by controlling both energy intake and energy expenditure.
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA. zwang@salk.edu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Qi
authors.forename: Anna
authors.initials: A
authors.lastname: Krones
authors.forename: Pamela
authors.initials: P
authors.lastname: Woodring
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhu
authors.forename: Janardan K
authors.initials: JK
authors.lastname: Reddy
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Evans
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
authors.forename: Tony
authors.initials: T
authors.lastname: Hunter
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000254:growth & development; D000818:Animals; D001481:Basal Metabolism / Q000235:genetics; D015152:Blotting, Northern; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D004435:Eating / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics* / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000235:genetics*; D051548:Histone Acetyltransferases / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics* / Q000502:physiology; D020738:Leptin / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D022722:Thermogenesis / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
chemical_list: D017931:DNA Primers; D020738:Leptin; D015534:Trans-Activators; D014157:Transcription Factors; D014280:Triglycerides; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; C538867:Ncoa3 protein, mouse; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3