Research Papers: Gerotarget (Focus on Aging):
Apigenin enhances skeletal muscle hypertrophy and myoblast differentiation by regulating Prmt7
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Young Jin Jang1,*, Hyo Jeong Son1,*, Yong Min Choi1, Jiyun Ahn1,2, Chang Hwa Jung1,2 and Tae Youl Ha1,2
1 Division of Nutrition and Metabolism Research, Korea Food Research Institute, Seongnam, Republic of Korea
2 Division of Food Biotechnology, University of Science and Technology, Daejeon, Republic of Korea
* These authors have contributed equally to this work
Tae Youl Ha, email:
Keywords: apigenin, Prmt7, GPR56, skeletal muscle hypertrophy, myoblast differentiation, Gerotarget
Received: March 24, 2017 Accepted: August 27, 2017 Published: September 16, 2017
Apigenin, a natural flavone abundant in various plant-derived foods including parsley and celery, has been shown to prevent inflammation and inflammatory diseases. However, the effect of apigenin on skeletal muscle hypertrophy and myogenic differentiation has not previously been elucidated. Here, we investigated the effects of apigenin on quadricep muscle weight and running distance using C57BL/6 mice on an accelerating treadmill. Apigenin stimulated mRNA expression of MHC (myosin heavy chain) 1, MHC2A, and MHC2B in the quadricep muscles of these animals. GPR56 (G protein-coupled receptor 56) and its ligand collagen III were upregulated by apigenin supplementation, together with enhanced PGC-1α, PGC-1α1, PGC-1α4, IGF1, and IGF2 expression. Prmt7 protein expression increased in conjunction with Akt and mTORC1 activation. Apigenin treatment also upregulated FNDC5 (fibronectin type III domain containing 5) mRNA expression and serum irisin levels. Furthermore, apigenin stimulated C2C12 myogenic differentiation and upregulated total MHC, MHC2A, and MHC2B expression. These events were attributable to an increase in Prmt7-p38-myoD expression and Akt and S6K1 phosphorylation. We also observed that Prmt7 regulates both PGC-1α1 and PGC-1α4 expression, resulting in a subsequent increase in GPR56 expression and mTORC1 activation. Taken together, these findings suggest that apigenin supplementation can promote skeletal muscle hypertrophy and myogenic differentiation by regulating the Prmt7-PGC-1α-GPR56 pathway, as well as the Prmt7-p38-myoD pathway, which may contribute toward the prevention of skeletal muscle weakness.
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