Acetoacetate Accelerates Muscle Regeneration and Ameliorates Muscular Dystrophy in Mice

作者：Xiaoting Zou, Jiao Meng, Li Li, Wanhong Han, Changyin Li, Ran Zhong, Xuexia Miao, Jun Cai, Yong Zhang, Dahai Zhu · 发表于：Journal of Biological Chemistry · 年份：2015 · DOI：10.1074/jbc.m115.676510 · 被引用次数：74 · 研究领域：Cancer, Hypoxia, and Metabolism、Mitochondrial Function and Pathology、Adipose Tissue and Metabolism

Acetoacetate (AA) is a ketone body and acts as a fuel to supply energy for cellular activity of various tissues. Here, we uncovered a novel function of AA in promoting muscle cell proliferation. Notably, the functional role of AA in regulating muscle cell function is further evidenced by its capability to accelerate muscle regeneration in normal mice, and it ameliorates muscular dystrophy in mdx mice. Mechanistically, our data from multiparameter analyses consistently support the notion that AA plays a non-metabolic role in regulating muscle cell function. Finally, we show that AA exerts its function through activation of the MEK1-ERK1/2-cyclin D1 pathway, revealing a novel mechanism in which AA serves as a signaling metabolite in mediating muscle cell function. Our findings highlight the profound functions of a small metabolite as signaling molecule in mammalian cells.