肝脏糖异生是维持血糖稳态的重要机制，其紊乱与糖尿病的发生发展密切相关。Metrnl是本课题组2014年发现的一个代谢调控新蛋白。Metrnl可被脂肪组织所分泌并调控脂肪细胞分化，并改善胰岛素抵抗。最近，我们发现metrnl在肝脏的糖代谢尤其是糖异生过程中可能发挥着关键的作用。在本课题中，拟用loxp-cre系统制备的肝脏特异性metrnl敲除小鼠模型，进行以下研究：(1)考察肝脏特异性metrnl敲除对基本代谢情况如体重、新陈代谢速率等的影响；(2)明确肝脏特异性metrnl敲除对肝脏的糖异生过程的影响；(3)探索metrnl调控肝脏糖异生的潜在信号分子通路；(4)阐明metrnl在糖尿病状态下的肝脏异常糖异生中及降糖药物二甲双胍抑制肝脏糖异生作用中的意义。这些研究可明确metrnl在肝脏糖异生中的重要作用及机制，有望为肝脏糖异生提供新的科学认识，并发现潜在的糖尿病药物干预新靶点。

Hepatic gluconeogenesis, an important event for maintaining blood glucose, is associated with the occurrence and development of diabetes mellitus. Metrnl, which was discovered by our group in 2014, is a novel metabolic regulatory protein. Our previous studies have demonstrated that metrnl can be secreted by adipose tissue, and regulates the adipocytes differentiation and thereby modulates insulin sensitivity. Recently, we found that metrnl may play a key role in the hepatic gluconeogenesis, which needs further investigation. We intend to perform the following studies using liver specific metrnl knockout mice: (1) comparing the basic metabolic conditions such as the body weight and metabolic rate in liver specific metrnl knock mice; (2) investigating the influence of liver specific metrnl knock on gluconeogenic capacity; (3) clarifying the molecular signaling pathways involved in the regulation of metrnl on hepatic gluconeogenesis; (4) demonstrating the involvement of metrnl in the abnormal diabetic condition. Overall, the present study may reveal a new metabolic regulatory role of metrnl, and provide a novel therapeutic target for treatment of diabetes.