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FoxO1 regulates muscle fiber-type specification and inhibits calcineurin signaling during C2C12 myoblast differentiation

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Abstract

Adult skeletal muscle fibers can be categorized into slow-oxidative and fast-glycolytic subtypes based on specialized metabolic and contractile properties. The Forkhead box O1 (FoxO1) transcription factor governs muscle growth, metabolism, and cell differentiation, and has been shown to be involved in regulating muscle fiber type specification. However, to date, the mechanism behind FoxO1-mediated fiber type diversity is still unclear. In this article, FoxO1 being expressed preferentially in fast twitch fiber enriched muscles is reported. Moreover, the autors also detected that FoxO1 expression decreased in both fast and slow muscles from mice undergoing endurance exercise which induced a fast-to-slow fiber type transition. Using C2C12 myoblast, constitutively active FoxO1 mutant altered the proportion of muscle fiber type composition toward a fast-glycolytic phenotype and attenuated calcineurin phosphatase activity. In addition, a transcriptionally inactive FoxO1 by resveratrol triggered the expression of genes related to slow-oxidative muscle but not sufficient to induce a complete slow fiber transformation. Taken together, these results suggest that FoxO1 up-regulates fast fiber-type formation and down-regulates muscle oxidative capacity at least in part through inhibition of the calcineurin pathway.

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Acknowledgments

This study was supported by Major Projects for Genetically Modified Organisms Breeding (No. 2009ZX08009-157B). We thank Professor Haojie Huang (Minnesota University, USA) for the kind donation of FoxO1-WT and FoxO1-A3 plasmids. We also thank Post Ph.D Qingwu Shen for his kind help in the revision of the original manuscript.

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  1. Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, 22 Xinong Road, Yangling, Xianyang, 712100, Shaanxi, China

    Yuan Yuan, Xin-e Shi, Yue-guang Liu & Gong-she Yang

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  1. Yuan Yuan
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  2. Xin-e Shi
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  3. Yue-guang Liu
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Correspondence to Gong-she Yang.

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Yuan, Y., Shi, Xe., Liu, Yg. et al. FoxO1 regulates muscle fiber-type specification and inhibits calcineurin signaling during C2C12 myoblast differentiation. Mol Cell Biochem 348, 77–87 (2011). https://doi.org/10.1007/s11010-010-0640-1

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