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Publication : Acetoacetate Accelerates Muscle Regeneration and Ameliorates Muscular Dystrophy in Mice.

First Author  Zou X Year  2016
Journal  J Biol Chem Volume  291
Issue  5 Pages  2181-95
PubMed ID  26645687 Mgi Jnum  J:275961
Mgi Id  MGI:6305673 Doi  10.1074/jbc.M115.676510
Citation  Zou X, et al. (2016) Acetoacetate Accelerates Muscle Regeneration and Ameliorates Muscular Dystrophy in Mice. J Biol Chem 291(5):2181-95
abstractText  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.
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