| First Author | Nam D | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 11239 | PubMed ID | 26058812 |
| Mgi Jnum | J:233551 | Mgi Id | MGI:5784958 |
| Doi | 10.1038/srep11239 | Citation | Nam D, et al. (2015) Novel Function of Rev-erbalpha in Promoting Brown Adipogenesis. Sci Rep 5:11239 |
| abstractText | Brown adipose tissue is a major thermogenic organ that plays a key role in maintenance of body temperature and whole-body energy homeostasis. Rev-erbalpha, a ligand-dependent nuclear receptor and transcription repressor of the molecular clock, has been implicated in the regulation of adipogenesis. However, whether Rev-erbalpha participates in brown fat formation is not known. Here we show that Rev-erbalpha is a key regulator of brown adipose tissue development by promoting brown adipogenesis. Genetic ablation of Rev-erbalpha 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-erbalpha 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-erbalpha activity promotes, whereas its inhibition suppresses brown adipocyte differentiation. Mechanistic investigations reveal that Rev-erbalpha represses key components of the TGF-beta cascade, an inhibitory pathway of brown fat development. Collectively, our findings delineate a novel role of Rev-erbalpha in driving brown adipocyte development, and provide experimental evidence that pharmacological interventions of Rev-erbalpha may offer new avenues for the treatment of obesity and related metabolic disorders. |
