A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
- PMID: 22237023
- PMCID: PMC3522098
- DOI: 10.1038/nature10777
A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
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.
Conflict of interest statement
The authors have no financial interest to disclose.
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Comment in
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Basic research: Irisin--behind the benefits of exercise.Nat Rev Endocrinol. 2012 Jan 31;8(4):195. doi: 10.1038/nrendo.2012.11. Nat Rev Endocrinol. 2012. PMID: 22290362 No abstract available.
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Metabolic disease: Exercise hormone fights metabolic disease.Nat Rev Drug Discov. 2012 Feb 17;11(3):189. doi: 10.1038/nrd3686. Nat Rev Drug Discov. 2012. PMID: 22338642 No abstract available.
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Irisin, turning up the heat.Cell Metab. 2012 Mar 7;15(3):277-8. doi: 10.1016/j.cmet.2012.02.010. Cell Metab. 2012. PMID: 22405065
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Is irisin a human exercise gene?Nature. 2012 Aug 30;488(7413):E9-10; discussion E10-1. doi: 10.1038/nature11364. Nature. 2012. PMID: 22932392 No abstract available.
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