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

        ( Jy Huh ),( F Din Cer ),( E Mesfum ),( Cs Mantzoros ) 전남대학교 약품개발연구소 2014 약품개발연구지 Vol.23 No.-

        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 FNOC5 expression in muscle and drive the browning of white ;ldipocytes in mice, implying that irisin may be rel;lted to muscle growth in addition to its beneficial effects in ;ldipocytes. In humans, the effect of irisin in muscle hypertrophy as well as adipocyte met;lbolism has not been fully investigated. METHODS: Primary cultured human myocytes/adipocytes and 3T3-L 1 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 PGC10 and myogenin expression. Irisin treatment significantly increased insulin-like growth factor 1 and decreased myostatin gene expression through ERK pathway. PGC104, a newly discovered PGCla 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 nd 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/FNOC5 has a pleiotropic role in muscle and improvement of adipocyte metabolism in humans. International Journal of Obesity (2014) 38, 1538-1544; doi:l0.l038/ijo.2014.42

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