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, leading to the loss of muscle function, and contributing to the global burden of these diseases. However, the underlying mechanisms behind the impairment are not well defined. Here we identify mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) as a critical regulator of skeletal muscle regeneration. Specifically, it regulates myogenic markers and myoblast differentiation by controlling mitochondrial biogenesis via CaMKKβ/AMPK. mGPDH deletion (mGPDH-/-) attenuated skeletal muscle regeneration in vitro and in vivo while mGPDH overexpression improved the insufficient regeneration 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 (HFD, ob/ob) and diabetic (STZ) mice by AAV led to a significant improvement in their muscle regeneration (Figure 1). Our study provides a new mechanism and potential therapeutic target for skeletal muscle regeneration impairment.


H. Qu: None. Y. Zheng: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.