FUNCTION OF AMP-ACTIVATED PROTEIN KINASE IN MYOGENESIS
Proper skeletal muscle development is crucial for human health and meat production. AMPK is the master metabolism regulator, but the role of AMPK in myogenesis remains poorly defined. Previous studies using AMPK activators revealed a negative regulatory role of AMPK in muscle development. However, metabolic disorders like obesity and type II diabetes are usually associated with reduced AMPK activity, not hyper activation. In this dissertation several studies were conducted to address the impact of AMPK inhibition on myogenesis. In the first study, the catalytic subunit AMPKα1 or AMPKα2 was deleted in myoblasts to study their differential roles in myogenesis. It was found that AMPKα1 promotes myogenesis through enhancing myogenin expression. In the second study, the mechanism underlying the effect of AMPKα1 on myogenesis was further explored. And it was found that AMPK promotes myogenin expression through inhibiting HDAC5 function, which facilitates myogenin gene transcription. In the third study, the change in muscle regeneration in obese mice and mice with systematic AMPKα1 KO or satellite cell-specific AMPKα1 KO were further explored. Muscle regeneration is attenuated due to obesity, mainly because of reduced AMPKα1 activity in skeletal muscle and more specifically satellite cells. In the fourth study, experiments were conducted to elucidate mechanisms leading to the reduced satellite cell number in obese and AMPKα1 knockout mice. An AMPKα1 mediated metabolic activation was found to be important in satellite cell activation and proliferation induced by muscle injury. Collectively, results of these studies revealed that AMPK facilitates myogenesis and its inhibition due to obesity impairs myogenesis and muscle regeneration. Thus, AMPK is a good target to promote muscle regeneration and muscle development and growth in diseases associated with reduced AMPK activity.