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Adipocyte and Cell Biology

Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans

International Journal of Obesity volume 38, pages 1538–1544 (2014)Cite this article

Subjects

Abstract

Background:

Irisin is a recently identified exercise-induced myokine suggested to induce browning of white adipocytes. Deficiency of myostatin, and thus stimulation of muscle growth, has also been reported to induce irisin and its precursor FNDC5 expression in muscle and drive the browning of white adipocytes in mice, implying that irisin may be related to muscle growth in addition to its beneficial effects in adipocytes. In humans, the effect of irisin in muscle hypertrophy as well as adipocyte metabolism has not been fully investigated.

Methods:

Primary cultured human myocytes/adipocytes and 3T3-L1 cells were used to examine irisin-regulated gene/protein expression. Lipid accumulation, ATP content, glycolysis, lipolysis and metabolite profile were measured in control and irisin-treated (10 and 50 nM) adipocytes.

Results:

In human myocytes, FNDC5 mRNA and irisin secretion were increased during myogenic differentiation, along with PGC1α and myogenin expression. Irisin treatment significantly increased insulin-like growth factor 1 and decreased myostatin gene expression through ERK pathway. PGC1α4, a newly discovered PGC1α isoform specifically related to muscle hypertrophy, was also upregulated. In human adipocytes, irisin induced uncoupling protein 1 and consequently increased adipocyte energy expenditure, expression of metabolic enzymes and metabolite intermediates, resulting in inhibition of lipid accumulation. Irisin and FNDC5 treatment also reduced preadipocyte differentiation, suggesting an additional mechanism in suppressing fat mass.

Conclusions:

These results suggest that irisin/FNDC5 has a pleiotropic role in muscle and improvement of adipocyte metabolism in humans.

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Acknowledgements

JYH researched data and wrote the manuscript. FD and EM researched data and reviewed the manuscript. CM designed the studies, supervised laboratory measurements and reviewed/edited the manuscript.

JYH is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

This study was supported by Award Number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development.

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Authors and Affiliations

  1. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    J Y Huh, F Dincer, E Mesfum & C S Mantzoros

  2. Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA

    C S Mantzoros

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  1. J Y Huh
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Correspondence to C S Mantzoros.

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Huh, J., Dincer, F., Mesfum, E. et al. Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans. Int J Obes 38, 1538–1544 (2014). https://doi.org/10.1038/ijo.2014.42

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