JOURNAL ARTICLE

A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis

Pontus Boström, Jun Wu, Mark P Jedrychowski, Anisha Korde, Li Ye, James C Lo, Kyle A Rasbach, Elisabeth Almer Boström, Jang Hyun Choi, Jonathan Z Long, Shingo Kajimura, Maria Cristina Zingaretti, Birgitte F Vind, Hua Tu, Saverio Cinti, Kurt Højlund, Steven P Gygi, Bruce M Spiegelman
Nature 2012 January 11, 481 (7382): 463-8
22237023
Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-γ co-activator-1 α (PGC1-α). Here we show in mouse that PGC1-α expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.

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