肝细胞因子Fetuin B介导肥胖状态下糖脂代谢异常的机制研究

肥胖等相关代谢疾病已成为世界性健康问题，造成了巨大的经济负担。肝细胞因子Fetuin B是近年发现的胎球蛋白家族新成员。有研究指出Fetuin B与非酒精性脂肪肝和糖尿病相关，然而在肥胖及糖脂代谢紊乱中的作用并不明确。我们前期研究发现，人群Fetuin B水平不仅与糖脂代谢紊乱密切相关，还与胰岛素抵抗风险增加相关；肥胖小鼠肝脏及血清Fetuin B水平显著升高，敲降肝脏Fetuin B可改善肥胖小鼠的超重、糖脂代谢异常及胰岛素抵抗；同时，敲降Fetuin B可缓解棕榈酸诱导的肝细胞脂质蓄积。由此，我们提出科学假说：Fetuin B通过调控胰岛素抵抗影响肥胖及糖脂代谢紊乱的发生发展。我们将进一步从动物、细胞和分子层面，明确Fetuin B在肥胖及糖脂代谢紊乱中的作用，阐明Fetuin B介导胰岛素抵抗的分子机制。本研究将从Fetuin B这个新视角出发，为肥胖等代谢性疾病的防治提供新的思路。

Metabolic-related diseases such as obesity have become a worldwide health problem and brought a huge burden to the economy. Hepatokine Fetuin B is a newly discovered member of the fetuin family. Several research have demonstrated that Fetuin B is associated with non-alcoholic fatty liver and diabetes, but its role in obesity and accompanying glucose and lipid metabolism disorders remains obscure. It is revealed in our previous cross-sectional study that serum Fetuin B level was not only closely related to glucose and lipid metabolic disorders, but also positively correlated with increased risk of insulin resistance. Further in vivo study showed that Fetuin B in the liver and serum were significantly increased in high fat diet induced obese mice. Knocking down Fetuin B in the liver could reduce bodyweight, ameliorate abnormal glucose and lipid metabolism and insulin resistance in obese mice. Moreover, knocking down Fetuin B in vitro could prevent palmitate induced lipid accumulation in hepatocyte cell. Thus, we hypothesized that Fetuin B might contribute to obesity and glycolipid metabolic disorders by regulating insulin resistance. To verify this hypothesis, we will further apply in vivo and in vitro studies to confirm the role of Fetuin B in regulating obesity and glycolipid metabolism and clarify the molecular mechanisms mediating regulation of Fetuin B on insulin resistance. Herein, by targeting the novel hepatokine Fetuin B, this study will provide a novel perspective for the pathogenesis and treatment of obesity and related metabolic diseases.