Mechanisms of Exercise Induced Hepatokine Secretion

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Exercise causes marked changes in the ability of tissues such as skeletal muscle and adipose (fat) to use carbohydrate and lipids as a fuel source. It is becoming increasingly clear that the regulation of this complex process involves circulating factors and hormones. Of great interest to the study of exercise physiology/biochemistry it has recently been reported that exercise leads to increases in the secretion of hormones from the liver. These hormones have been called "hepatokines". The secretion of these factors is thought to play an important role in modulating the effects of exercise on muscle and adipose tissue fuel metabolism. Surprisingly, little is known regarding the specific mechanisms which control the secretion of these factors from liver during exercise. The purpose of the current project is to determine the systemic factors and the underlying mechanisms through which exercise controls hepatokine content and secretion. To address this broad research question we will use a combination of cell culture techniques in combination with genetically modified mice. We believe that a hormone called glucagon and the activation of the enzyme 5'AMP activated protein kinase (AMPK) are involved in this process. The experiments that are outlined in this application will provide novel information about how the liver responds to exercise and in turn will provide important insight into the integration of liver, muscle and adipose tissue metabolism. In addition, the proposed research program will provide an outstanding training environment for HQP.