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

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.

Pubmed ID: 22237023

Authors

  • Boström P
  • Wu J
  • Jedrychowski MP
  • Korde A
  • Ye L
  • Lo JC
  • Rasbach KA
  • Boström EA
  • Choi JH
  • Long JZ
  • Kajimura S
  • Zingaretti MC
  • Vind BF
  • Tu H
  • Cinti S
  • Højlund K
  • Gygi SP
  • Spiegelman BM

Journal

Nature

Publication Data

January 26, 2012

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK31405
  • Agency: NIDDK NIH HHS, Id: DK54477
  • Agency: NIDDK NIH HHS, Id: K99 DK087853
  • Agency: NIDDK NIH HHS, Id: P30 DK057521
  • Agency: NIDDK NIH HHS, Id: R01 DK054477
  • Agency: NIDDK NIH HHS, Id: R01 DK061562
  • Agency: NIDDK NIH HHS, Id: R37 DK031405

Mesh Terms

  • Adipocytes
  • Adipose Tissue, Brown
  • Adipose Tissue, White
  • Animals
  • Cell Respiration
  • Cells, Cultured
  • Culture Media, Conditioned
  • Energy Metabolism
  • Exercise
  • Gene Expression Regulation
  • Hormones
  • Humans
  • Insulin Resistance
  • Intracellular Signaling Peptides and Proteins
  • Ion Channels
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Mitochondrial Proteins
  • Models, Animal
  • Muscle Cells
  • Obesity
  • Physical Conditioning, Animal
  • Plasma
  • Subcutaneous Fat
  • Thermogenesis
  • Trans-Activators
  • Transcription Factors