White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis |
| |
Authors: | Cao Lei Choi Eugene Y Liu Xianglan Martin Adam Wang Chuansong Xu Xiaohua During Matthew J |
| |
Affiliation: | Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA. lei.cao@osumc.edu |
| |
Abstract: | Living in an enriched environment with complex physical and social stimulation leads to improved cognitive and metabolic health. In white fat, enrichment induced the upregulation of the brown fat cell fate determining gene Prdm16, brown fat-specific markers, and genes involved in thermogenesis and β-adrenergic signaling. Moreover, pockets of cells with prototypical brown fat morphology and high UCP1 levels were observed in the white fat of enriched mice associated with resistance to diet-induced obesity. Hypothalamic overexpression of BDNF reproduced the enrichment-associated activation of the brown fat gene program and lean phenotype. Inhibition of BDNF signaling by genetic knockout or dominant-negative trkB reversed this phenotype. Our genetic and pharmacologic data suggest a mechanism whereby induction of hypothalamic BDNF expression in response to environmental stimuli leads to selective sympathoneural modulation of white fat to induce "browning" and increased energy dissipation. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|