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Mitochondrial glycerol 3-phosphate dehydrogenase promotes skeletal muscle regeneration.


ABSTRACT: While adult mammalian skeletal muscle is stable due to its post-mitotic nature, muscle regeneration is still essential throughout life for maintaining functional fitness. During certain diseases, such as the modern pandemics of obesity and diabetes, the regeneration process becomes impaired, which leads to the loss of muscle function and contributes to the global burden of these diseases. However, the underlying mechanisms of the impairment are not well defined. Here, we identify mGPDH as a critical regulator of skeletal muscle regeneration. Specifically, it regulates myogenic markers and myoblast differentiation by controlling mitochondrial biogenesis via CaMKK?/AMPK. mGPDH-/- attenuated skeletal muscle regeneration in vitro and in vivo, while mGPDH overexpression ameliorated dystrophic pathology in mdx mice. Moreover, in patients and animal models of obesity and diabetes, mGPDH expression in skeletal muscle was reduced, further suggesting a direct correlation between its abundance and muscular regeneration capability. Rescuing mGPDH expression in obese and diabetic mice led to a significant improvement in their muscle regeneration. Our study provides a potential therapeutic target for skeletal muscle regeneration impairment during obesity and diabetes.

SUBMITTER: Liu X 

PROVIDER: S-EPMC6284384 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Mitochondrial glycerol 3-phosphate dehydrogenase promotes skeletal muscle regeneration.

Liu Xiufei X   Qu Hua H   Zheng Yi Y   Liao Qian Q   Zhang Linlin L   Liao Xiaoyu X   Xiong Xin X   Wang Yuren Y   Zhang Rui R   Wang Hui H   Tong Qiang Q   Liu Zhenqi Z   Dong Hui H   Yang Gangyi G   Zhu Zhiming Z   Xu Jing J   Zheng Hongting H  

EMBO molecular medicine 20181201 12


While adult mammalian skeletal muscle is stable due to its post-mitotic nature, muscle regeneration is still essential throughout life for maintaining functional fitness. During certain diseases, such as the modern pandemics of obesity and diabetes, the regeneration process becomes impaired, which leads to the loss of muscle function and contributes to the global burden of these diseases. However, the underlying mechanisms of the impairment are not well defined. Here, we identify mGPDH as a crit  ...[more]

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