Wang 2019 EMBO Rep

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Wang T, Xu YQ, Yuan YX, Xu PW, Zhang C, Li F, Wang LN, Yin C, Zhang L, Cai XC, Zhu CJ, Xu JR, Liang BQ, Schaul S, Xie PP, Yue D, Liao ZR, Yu LL, Luo L, Zhou G, Yang JP, He ZH, Du M, Zhou YP, Deng BC, Wang SB, Gao P, Zhu XT, Xi QY, Zhang YL, Shu G, Jiang QY (2019) Succinate induces skeletal muscle fiber remodeling via SUNCR1 signaling pathway. EMBO Rep [Epub ahead of print].

» PMID: 31318145 Open Access

Wang T*, Xu YQ, Yuan YX, Xu PW, Zhang C, Li F, Wang LN, Yin C, Zhang L, Cai XC, Zhu CJ, Xu JR, Liang BQ, Schaul S, Xie PP, Yue D, Liao ZR, Yu LL, Luo L, Zhou G, Yang JP, He ZH, Du M, Zhou YP, Deng BC, Wang SB, Gao P, Zhu XT, Xi QY, Zhang YL, Shu G, Jiang QY (2019) EMBO Rep

Abstract: The conversion of skeletal muscle fiber from fast twitch to slow-twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber-type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss-of-function models generated by phospholipase Cβ antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius-specific knockdown, we found that the effects of succinate on skeletal muscle fiber-type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate-based compounds in both athletic and sedentary populations.

© 2019 The Authors. Published under the terms of the CC BY 4.0 license.

Keywords: SUNCR1, Aerobic exercise, Fiber type, Skeletal muscle, Succinate Bioblast editor: Plangger M


Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style 


Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Intact cells 

Regulation: Substrate 


HRR: Oxygraph-2k 

Labels, 2019-08