title: Novel Function of Rev-erbα in Promoting Brown Adipogenesis.
abstract: Brown adipose tissue is a major thermogenic organ that plays a key role in maintenance of body temperature and whole-body energy homeostasis. Rev-erbα, a ligand-dependent nuclear receptor and transcription repressor of the molecular clock, has been implicated in the regulation of adipogenesis. However, whether Rev-erbα participates in brown fat formation is not known. Here we show that Rev-erbα is a key regulator of brown adipose tissue development by promoting brown adipogenesis. Genetic ablation of Rev-erbα in mice severely impairs embryonic and neonatal brown fat formation accompanied by loss of brown identity. This defect is due to a cell-autonomous function of Rev-erbα in brown adipocyte lineage commitment and terminal differentiation, as demonstrated by genetic loss- and gain-of-function studies in mesenchymal precursors and brown preadipocytes. Moreover, pharmacological activation of Rev-erbα activity promotes, whereas its inhibition suppresses brown adipocyte differentiation. Mechanistic investigations reveal that Rev-erbα represses key components of the TGF-β cascade, an inhibitory pathway of brown fat development. Collectively, our findings delineate a novel role of Rev-erbα in driving brown adipocyte development, and provide experimental evidence that pharmacological interventions of Rev-erbα may offer new avenues for the treatment of obesity and related metabolic disorders.
authors.affiliation: Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX, 77030.
authors.forename: Deokhwa
authors.initials: D
authors.lastname: Nam
authors.affiliation: Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX, 77030.
authors.forename: Somik
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Department of Cardiovascular Medicine, Second Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei, 050017, China.
authors.forename: Hongshan
authors.initials: H
authors.lastname: Yin
authors.affiliation: Diabetes and Endocrinology Research Center, Department of Medicine, Baylor College of Medicine, Houston, TX, 77030.
authors.forename: Ruya
authors.initials: R
authors.lastname: Liu
authors.affiliation: Diabetes and Endocrinology Research Center, Department of Medicine, Baylor College of Medicine, Houston, TX, 77030.
authors.forename: Jeongkyung
authors.initials: J
authors.lastname: Lee
authors.affiliation: Diabetes and Endocrinology Research Center, Department of Medicine, Baylor College of Medicine, Houston, TX, 77030.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Yechoor
authors.affiliation: Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX, 77030.
authors.forename: Ke
authors.initials: K
authors.lastname: Ma
mesh_terms: D002001:Adipose Tissue, Brown / Q000166:cytology / Q000254:growth & development*; D000818:Animals; D002454:Cell Differentiation; D015694:Gene Products, rev / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D015694:Gene Products, rev