肝脏是维持代谢平衡的一个重要器官。肝脏功能失调可诱发高血脂、肥胖、糖尿病等常见代谢疾病，并增加心血管疾病如中风、心肌梗死和心力衰竭发生的危险性。Hepsin是一种在肝脏中高表达的II型跨膜丝氨酸蛋白酶，迄今其生理功能仍然不清楚。我们的前期研究表明，hepsin 能够在肝脏通过活化肝细胞生长因子 (hepatocyte growth factor)，激活其下游分子通路，从而促进肝糖原和脂质合成。Hepsin 敲除小鼠血糖和肝糖原水平降低，并且有抗高脂饮食导致肥胖和脂肪肝的表型。本研究将通过生物化学、细胞生物学和小鼠模型实验来揭示hepsin在肝脏中的功能。本项研究将有助于揭示调控肝脏葡萄糖和脂类代谢稳态调控的新分子机理，以及该机理失常在高血脂、肥胖、糖尿病等代谢疾病中的作用。我们的研究对重大心血管和代谢性疾病的防治有重要意义。

The liver plays an important role in regulating metabolic homeostasis. Dysregulated liver function may lead to common metabolic diseases such as hyperlipidemia, obesity and diabetes, thereby increasing the risk of cardiovascular diseases such as stroke, myocardial infarction and heart failure. Hepsin is a type II transmembrane serine protease highly expressed in the liver. To date, the physiological function of hepsin in the liver remains unknown. Our preliminary studies indicate that hepsin may activate hepatocyte growth factor (HGF) in the liver and stimulate the HGF down-stream pathway, thereby promoting hepatic glycogen and lipid synthesis. Hepsin knockout mice had low levels of blood glucose and liver glycogen and were resistant to high-fat diet-induced obesity and fatty liver. In this project, we plan to conduct biochemical, cell biology and mouse model studies to elucidate the function of hepsin in the liver. Our studies should help to identify new molecular mechanisms in regulating glucose and lipid metabolism in the liver and to understand the role of such mechanisms in hyperlipidemia, obesity and diabetes. Such studies should be of great importance for the prevention and treatment of major cardiovascular and metabolic diseases.