cyclin-d1 and Muscular-Dystrophy--Animal

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.

Topics: Acetoacetates; Animals; Cell Proliferation; Cyclin D1; Disease Models, Animal; Gene Expression Regulation; Ketone Bodies; MAP Kinase Kinase 1; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Muscle, Skeletal; Muscular Dystrophy, Animal; Regeneration; Satellite Cells, Skeletal Muscle; Signal Transduction