Lipin1, an intracellular protein, plays critical roles in controlling lipid synthesis and energy metabolism through its enzymatic activity and nuclear transcriptional functions. Several mouse models of skeletal muscle wasting are associated with lipin1 mutation or altered expression. Recent human studies have suggested that children with homozygous null mutations in the LPIN1 gene suffer from rhabdomyolysis. However, the underlying pathophysiologic mechanism is still poorly understood. In the present study we examined whether lipin1 contributes to regulating muscle regeneration. We characterized the time course of skeletal muscle regeneration in lipin1-deficient fld mice after injury. We found that fld mice exhibited smaller regenerated muscle fiber cross-sectional areas compared with wild-type mice in response to injury. Our results from a series of in vitro experiments suggest that lipin1 is up-regulated and translocated to the nucleus during myoblast differentiation and plays a key role in myogenesis by regulating the cytosolic activation of ERK1/2 to form a complex and a downstream effector cyclin D3-mediated cell cycle withdrawal. Overall, our study reveals a previously unknown role of lipin1 in skeletal muscle regeneration and expands our understanding of the cellular and molecular mechanisms underlying skeletal muscle regeneration.

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Published in The Journal of Biological Chemistry, v. 290, no. 39, p. 23646-23655.

This research was originally published in The Journal of Biological Chemistry. Weihua Jiang, Jing Zhu, Xun Zhuang, Xiping Zhang, Tao Luo, Karyn A. Esser, and Hongmei Ren. Lipin1 Regulates Skeletal Muscle Differentiation through Extracellular Signal-regulated Kinase (ERK) Activation and Cyclin D Complex-Regulated Cell Cycle Withdrawal. The Journal of Biological Chemistry. 2015; 290:23646-23655. © the American Society for Biochemistry and Molecular Biology.

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This work was supported, in whole or in part, by National Institutes of Health Grants P20 GM103527-06 (Center of Biomedical Research Excellence on Obesity and Cardiovascular Diseases) and NIH AR061939 (to K. A. E.). This work was also supported by American Heart Association Beginning Grant-in-aid 11BGIA7710059 and National Scientist Development Grant 12SDG12050697 (to H. R.). The authors declare that they have no conflicts of interest with the contents of this article.