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Cell Metab. 2014 Feb 4;19(2):302-9. doi: 10.1016/j.cmet.2013.12.017.

Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans.

Author information

1
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
2
Surgery Branch, National Institutes of Health, Bethesda, MD 20892, USA.
3
Endocrine Oncology Branch, National Institutes of Health, Bethesda, MD 20892, USA.
4
National Cancer Institute and Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
5
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: fsceli@vcu.edu.

Abstract

Rediscovery of cold-activated brown adipose tissue (BAT) in humans has boosted research interest in identifying BAT activators for metabolic benefits. Of particular interest are cytokines capable of fat browning. Irisin, derived from FNDC5, is an exercise-induced myokine that drives brown-fat-like thermogenesis in murine white fat. Here we explored whether cold exposure is an afferent signal for irisin secretion in humans and compared it with FGF21, a brown adipokine in rodents. Cold exposure increased circulating irisin and FGF21. We found an induction of irisin secretion proportional to shivering intensity, in magnitude similar to exercise-stimulated secretion. FNDC5 and/or FGF21 treatment upregulated human adipocyte brown fat gene/protein expression and thermogenesis in a depot-specific manner. These results suggest exercise-induced irisin secretion could have evolved from shivering-related muscle contraction, serving to augment brown fat thermogenesis in concert with FGF21. Irisin-mediated muscle-adipose crosstalk may represent a thermogenic, cold-activated endocrine axis that is exploitable in obesity therapeutics development.

PMID:
24506871
DOI:
10.1016/j.cmet.2013.12.017
[Indexed for MEDLINE]
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