Molecular mechanism of exercise training-induced skeletal muscle adaptation
Exercise training (physical activity) has been known since antiquity to promote physical performance and health and prevent disease. The benefits are largely mediated by responses and adaptations in skeletal muscle. Mitochondria, the cellular powerplants which oxidize nutrients and generate ATP, are responsible for meeting the energetic demand of exercise in skeletal muscle. It is well known that exercise training elicits profound mitochondrial remodeling through mitochondrial biogenesis (synthesis and incorporation of new mitochondrial proteins and DNA to expand the existing network), fission and fusion (structural separation and joining of mitochondria), as well as mitophagy (selective degradation of damaged/dysfunctional mitochondria). These processes occur to replace only suboptimal portions of the mitochondrial network, which is critical for optimal functional and metabolic improvements bearing paramount scientific and clinical values. Research in this laboratory has focused on two opposite processes: addition (biogenesis) and removal (mitophagy) of mitochondria in skeletal muscle. We investigate the role of mitogen-activated protein kinase (MAPK) p38 in exercise training-induced mitochondrial biogenesis through peroxisome proliferator activated receptor γ co-activator-1α (Pgc-1α) (NIH R01). More recently, we developed MitoTimer reporter gene and its reporter mouse, and elucidate the signaling mechanism of exercise-induced mitophagy through AMPK-Ulk1 regulatory axis (NIH R01). In addition, we investigate the regulation and functional role of mitochondria-associated bioenergetic sensor AMPK (mitoAMPK) in striated muscles and other tissues. Finally, we have recently patented and developed a novel mouse voluntary weightlifting model and study the activation of mTOR and autophagy mechineries in contractile and metabolic adaptation to resistance exercise (Read more). The overall goal of these research efforts is to elucidate the fundamental molecular and signaling mechanisms of exercise training-induced contractile and metabolic adaptations and lay a solid fundation for the development of more efficacious interventions to promote health and prevent and treat chronic diseases.
Exercise benefits in protection against diseases
Exercise training is considered the most effective intervention against the development of non-communicable diseases, including cardiovascular, metabolic and neurodegenerative diseases and cancer; however, scientific evidence with experimental proof are often missing, and the underlying mechanisms are less well understood. To this end, we take advantage of animal models with molecular genetics and the state-of-the-art imaging and functional analyese to gain improved understanding of the benefits of exercise training in diesease prevention. We investigate the role of endurance exercise training-induced EcSOD expression in skeletal muscle in protection against oxidative damage in skeletal muscle and other peripheral tissues/organs in various disease settings, including catabolic muscle wasting, diabetic cardiomyopathy and multiple organ dysfunction syndrome induced by endotoxemia and sepsis and trauma (NIH R01). We investigate the impact of endurance and resistance exercise training in Friedreich's ataxia mice (knockout and knock-in of Fxn, KIKO) with a focus on the symptomatic onset of the disease (FARA General Grant). Using a clinically relevant model of touniquet use in skeletal muscle in mice, we conduct research to understand the benefit of endurance exercise and the importance of preserving NMJ in functional muscle regeneration following ischemia-reperfusion. Finally, we are very interested in the imapct of exercise during pregnancy in preventing hypermethylation of the Pgc-1a gene in offspring skeletal muscle and the development of age-dependent metabolic dysfunction later in life (Read more). These and other collaborative projects will provide novel insights into the moledular mechanism by which exercise training elicits profound protection against the development of various diseases.