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Publication : White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis.

First Author  Cao L Year  2011
Journal  Cell Metab Volume  14
Issue  3 Pages  324-38
PubMed ID  21907139 Mgi Jnum  J:176656
Mgi Id  MGI:5292407 Doi  10.1016/j.cmet.2011.06.020
Citation  Cao L, et al. (2011) White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis. Cell Metab 14(3):324-38
abstractText  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 beta-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.
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