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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 Z, 2012. "A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis," Nature, Nature, vol. 481(7382), pages 463-468, January.
    • Handle: RePEc:nat:nature:v:481:y:2012:i:7382:d:10.1038_nature10777
    DOI: 10.1038/nature10777
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    Cited by:

    1. Jiangshan Liu & Bote Qi & Lin Gan & Yanli Shen & Yu Zou, 2022. "A Bibliometric Analysis of the Literature on Irisin from 2012–2021," IJERPH, MDPI, vol. 19(10), pages 1-16, May.
    2. Pedro L. Cosio & Manuel Crespo-Posadas & Álvaro Velarde-Sotres & Mireia Pelaez, 2021. "Effect of Chronic Resistance Training on Circulating Irisin: Systematic Review and Meta-Analysis of Randomized Controlled Trials," IJERPH, MDPI, vol. 18(5), pages 1-16, March.
    3. Zhijun Tan & Zengchun Ye & Jun Zhang & Yanru Chen & Cailian Cheng & Cheng Wang & Xun Liu & Tanqi Lou & Hui Peng, 2017. "Serum irisin levels correlated to peritoneal dialysis adequacy in nondiabetic peritoneal dialysis patients," PLOS ONE, Public Library of Science, vol. 12(4), pages 1-13, April.

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