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 and Bruce M. Spiegelman ()
Additional contact information
Pontus Boström: Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, Floor 11, Boston, Massachusetts 02115, USA
Jun Wu: Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, Floor 11, Boston, Massachusetts 02115, USA
Mark P. Jedrychowski: Harvard Medical School
Anisha Korde: Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, Floor 11, Boston, Massachusetts 02115, USA
Li Ye: Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, Floor 11, Boston, Massachusetts 02115, USA
James C. Lo: Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, Floor 11, Boston, Massachusetts 02115, USA
Kyle A. Rasbach: Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, Floor 11, Boston, Massachusetts 02115, USA
Elisabeth Almer Boström: Brigham and Women’s Hospital, Harvard Medical School
Jang Hyun Choi: Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, Floor 11, Boston, Massachusetts 02115, USA
Jonathan Z. Long: Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, Floor 11, Boston, Massachusetts 02115, USA
Shingo Kajimura: University of California
Maria Cristina Zingaretti: Università Politecnica delle Marche, Electron Microscopy Unit-Azienda Ospedali Riuniti, Ancona 60020, Italy
Birgitte F. Vind: Diabetes Research Center, Odense University Hospital, DK-5000, Odense, Denmark
Hua Tu: LakePharma, Inc., 530 Harbor Blvd, Belmont, California 94002, USA
Saverio Cinti: Università Politecnica delle Marche, Electron Microscopy Unit-Azienda Ospedali Riuniti, Ancona 60020, Italy
Kurt Højlund: Diabetes Research Center, Odense University Hospital, DK-5000, Odense, Denmark
Steven P. Gygi: Harvard Medical School
Bruce M. Spiegelman: Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, Floor 11, Boston, Massachusetts 02115, USA

Nature, 2012, vol. 481, issue 7382, 463-468

Abstract: Abstract 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.

Date: 2012
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DOI: 10.1038/nature10777

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