IGFBP-2对机体糖脂代谢的调控作用及机制研究

流行病学研究显示肥胖及相关代谢性疾病发病率显著增高，已成为危害公共健康的主要问题。胰岛素样生长因子结合蛋白2（IGFBP-2）主要在肝脏合成，胰腺、心肌及成熟的脂肪细胞有表达。上调IGFBP-2可以预防肥胖并延缓胰岛素抵抗的发生。我们前期研究显示IGFBP-2水平与代谢综合征的发生呈负相关，对糖脂代谢有正调节作用。细胞实验证明胰岛素通过PI3K/mTOR信号通路调控IGFBP-2表达。预实验发现IGFBP-2敲除小鼠的体重及血糖明显升高，高脂喂养引起小鼠肝脏及血浆中IGFBP-2表达降低。长期以来的研究提示：IGFBP-2在代谢性疾病的发生发展中具有重要的调控作用，但其内在的分子机制尚不明确。本研究拟使用肝脏特异性敲除IGFBP-2小鼠、腺病毒过表达IGFBP-2小鼠和细胞模型，揭示IGFBP-2在调控机体能量代谢、糖脂代谢过程中的关键作用及机制，为肥胖及相关代谢性疾病的诊治提供更多依据。

Epidemiological studies have shown that the increasing incidence of obesity and related metabolic diseases have negative impacts on public health. Insulin-like growth factor binding protein-2 (IGFBP-2), predominantly synthesized in the liver, is expressed in the pancreas, cardiac muscle, and mature adipocytes. Up-regulation of IGFBP-2 levels can prevent the development of obesity and delay the onset of insulin resistance. Our previous studies have found that IGFBP-2 levels were negatively correlated with the occurrence of metabolic syndrome and had a positive effect on glucose and lipid metabolism. In vitro studies have documented insulin-regulated IGFBP-2 expression via the PI3K/mTOR signaling pathway. Preliminary lab results have demonstrated significant increases in body weight and blood glucose levels in the IGFBP-2 knockout mice, while decreased IGFBP-2 expression in the liver and serum in the high-fat diet-induced obese mice. Long-term studies have constructed that IGFBP-2 plays an important role in the occurrence and development of metabolic diseases, yet the underlying molecular mechanisms are still unclear. This project is planning to investigate the role and mechanism of IGFBP-2 in regulating energy, glucose, and lipid metabolism by using liver-specific IGFBP-2 knockout and overexpression mice and cell models. This study will provide more evidence for the diagnosis and treatment of obesity and related metabolic diseases.