有氧运动能有效缓解非酒精性脂肪肝，但机制仍未明确。肝脏神经酰胺代谢紊乱是非酒精性脂肪肝发生发展的重要机制之一。连接肝脏与脂肪的FGF21-adiponectin通路在调控神经酰胺代谢中起重要作用。在前期研究中，我们发现有氧运动能够提高FGF21诱导adiponectin分泌的功能，据此推测有氧运动通过增加脂肪组织FGF21敏感性，促进adiponectin分泌，进而调节肝脏神经酰胺代谢，改善非酒精性脂肪肝。我们利用高脂饮食诱导非酒精性脂肪肝小鼠模型，研究有氧运动对肝脏神经酰胺代谢、FGF21-adiponectin通路的影响。在此基础上，采用FGF21基因敲除小鼠，深入探讨FGF21-adiponectin通路在有氧运动调节肝脏神经酰胺代谢，抗非酒精性脂肪肝中的作用。本课题将从“肝脏-脂肪组织对话”的视角探讨有氧运动改善非酒精性脂肪肝的机制，为运动抗非酒精性脂肪肝奠定理论基础。

The beneficial effects of aerobic exercise on nonalcoholic fatty liver disease have been generally reported. However, the precise mechanism remains unclear. Disorganized ceramide metabolism contributes to the development of nonalcoholic fatty liver disease. FGF21-adiponectin axis, which functions as the key mediator for the crosstalk between the liver and adipose tissue, plays an important role in the regulation of ceramide metabolism. Our previous study indicated that the function of FGF21 to increase adiponectin secretion was significantly improved by aerobic exercise. These findings led us to hypothesize that aerobic exercise might enhance FGF21 sensitivity in adipose tissue, promote adiponectin secretion, which may play a potential role in the improved hepatic ceramide metabolism, and thus ameliorate nonalcoholic fatty liver disease. To test the hypothesis, we will investigate the effects of aerobic exercise on hepatic ceramide metabolism and FGF21-adiponectin axis in a high-fat diet-induced nonalcoholic fatty liver disease model. We will furthermore use wild-type and FGF21-knockout mice to explore the role of FGF21-adiponectin axis in aerobic exercise-mediated improvements of hepatic ceramide metabolism and nonalcoholic fatty liver disease. From the perspective of the crosstalk between the liver and adipose tissue, we will have a better understanding of the mechanism by which aerobic exercise prevents nonalcoholic fatty liver disease.