AMP-Activated Protein Kinase α1 but Not α2 Catalytic Subunit Potentiates Myogenin Expression and Myogenesis

The link between AMP-activated protein kinase (AMPK) and myogenesis remains poorly defined. AMPK has two catalytic alpha subunits, alpha 1 and alpha 2. We postulated that AMPK promotes myogenesis in an isoform-specific manner. Primary myoblasts were prepared from AMPK knockout (KO) mice and AMPK conditional KO mice, and knockout of the alpha 1 but not the alpha 2 subunit resulted in downregulation of myogenin and reduced myogenesis. Myogenin expression and myogenesis were nearly abolished in the absence of both AMPK alpha 1 and AMPK alpha 2, while enhanced AMPK activity promoted myogenesis and myotube formation. The AMPK alpha 1-specific effect on myogenesis was likely due to the dominant expression of alpha 1 in myoblasts. These results were confirmed in C2C12 cells. To further evaluate the necessity of the AMPK alpha 1 subunit for myogenesis in vivo, we prepared both DsRed AMPK alpha 1 knockout myoblasts and enhanced green fluorescent protein (EGFP) wild-type myoblasts, which were cotransplanted into tibialis anterior muscle. A number of green fluorescent muscle fibers were observed, showing the fusion of engrafted wildtype myoblasts with muscle fibers; on the other hand, very few or no red muscle fibers were observed, indicating the absence of myogenic capacity of AMPK alpha 1 knockout myoblasts. In summary, these results indicate that AMPK activity promotes myogenesis through a mechanism mediated by AMPK alpha 1.