Physical exercise induces a profound alteration of energy metabolism in skeletal muscle as well as in other organs such as heart, liver, and adipose tissue, which contributes to its beneficial effects in combating metabolic diseases/syndromes and maintaining human health. For instance, a single bout of exercise can decrease the levels of blood glucose to the normal range in Type II diabetic patients, primarily through promoting uptake and utilization of glucose in skeletal muscle. Exercise also increases the breakdown of lipids (lipolysis) in adipose tissue and promotes fatty acid uptake and utilization in skeletal muscle and heart, which mediates its anti-obesity effects. A better understanding of energy metabolism regulation during exercise will shed lights on novel therapies for metabolic diseases and syndromes.
Our lab aims to identify and decipher cellular pathways that regulate energy metabolism during exercise in skeletal muscle and heart. Our research will focus on the regulation of two important cellular pathways that controls exercise-induced alteration in energy metabolism, the AMP-activated protein kinase (AMPK) signaling pathway and the autophagy process. AMPK is a master regulator of energy homeostasis, and is activated in response to cellular energy shortage. Upon activation, AMPK phosphorylates its substrates to enhance energy production and inhibit energy consumption, which helps restore energy balance. During exercise, AMPK is activated in skeletal muscle and heart, and plays a crucial role in promoting energy metabolism adaptation. Autophagy is a cellular process to degrade and recycle unnecessary and dysfunctional cell components. It plays an essential role in the maintenance of cellular homeostasis by removing harmful intracellular material, and by allowing reutilization of internal sources of nutrients under energy stress conditions, such as exercise. Autophagy level is dramatically induced in skeletal muscle and heart during exercise to facilitate energy metabolism adaptation. The AMPK signaling and autophagy are two independently regulated yet interlinked cellular pathways. Previous studies have demonstrated that AMPK activation upregulates autophagy. Recently, we have established a novel link that certain autophagy proteins and complexes are required for the effective AMPK activation in skeletal muscle during exercise. We will combine biochemical, cell biology, and molecular biology approaches and animal models to further reveal the novel regulations of AMPK signaling and autophagy during exercise in skeletal muscle and heart as well as the potential interplay between these two pathways, with an ultimate goal of advancing our understanding of exercise-induced energy metabolism adaptation and providing new angles for the prevention and treatment of metabolic syndromes and diseases. Our lab also seeks to understand the regulation of energy metabolism in other physiological/pathological conditions, such as myocardial ischemia/reperfusion.