Myogenin induces a shift of enzyme activity from glycolytic to oxidative metabolism in muscles of transgenic mice

Physical training regulates muscle metabolic and contractile properties by altering gene expression. Electrical activity evoked in muscle fiber membra ne during physical activity is crucial for such regulation, but the subsequ ent intracellular pathway is virtually unmapped, Here we investigate the ab ility of myogenin, a muscle-specific transcription factor strongly regulate d by electrical activity, to alter muscle phenotype. Myogenin was overexpre ssed in transgenic mice using regulatory elements that confer strong expres sion confined to differentiated post-mitotic fast muscle fibers. In fast mu scles from such mice, the activity levels of oxidative mitochondrial enzyme s were elevated two- to threefold, whereas levels of glycolytic enzymes wer e reduced to levels 0.3-0.6 times those found in wild-type mice. Histochemical analysis shows widespread increases in mitochondrial componen ts and glycogen accumulation. The changes in enzyme content were accompanie d by a reduction in fiber size, such that many fibers acquired a size typic al of oxidative fibers. No change in fiber type-specific myosin heavy chain isoform expression was observed. Changes in metabolic properties without c hanges in myosins are observed after moderate endurance training in mammals , including humans. Our data suggest that myogenin regulated by electrical activity may mediate effects of physical training on metabolic capacity in muscle.