Mechanisms of Exercise Induced Hepatokine Secretion

运动导致骨骼肌和脂肪（脂肪）等组织使用碳水化合物和脂质作为燃料来源的能力发生显著变化。越来越清楚的是，对这一复杂过程的调节涉及循环因子和激素。运动生理学/生物化学的研究引起了极大的兴趣，最近有报道说，运动导致肝脏激素分泌增加。这些激素被称为“肝因子”。这些因子的分泌被认为在调节运动对肌肉和脂肪组织燃料代谢的影响中起着重要作用。令人惊讶的是，人们对运动过程中控制肝脏分泌这些因子的具体机制知之甚少。当前项目的目的是确定运动控制肝因子含量和分泌的系统因素和潜在机制。为了解决这个广泛的研究问题，我们将使用细胞培养技术与转基因小鼠相结合。我们认为一种叫做胰高血糖素的激素和5'AMP活化蛋白激酶（AMPK）的激活参与了这个过程。本应用程序中概述的实验将提供有关肝脏如何对运动作出反应的新信息，反过来将为肝脏，肌肉和脂肪组织代谢的整合提供重要的见解。此外，拟议的研究计划将为HQP提供一个优秀的培训环境。

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.