肥胖是导致心脏功能损伤的重要原因之一，但机制仍未阐明。MicroRNAs在心脏发育及心血管疾病中发挥重要作用，且miR-208在心肌组织中高表达。我们的前期研究发现，高脂饮食诱导的肥胖小鼠心脏功能受损，伴有心肌miR-208升高及胰岛素受体底物2（IRS2）下调，然而机制仍不清楚，国内外未见报道。为此，我们提出假说：miR-208可能通过抑制IRS2/PI3K/Akt通路介导高脂饮食诱导的肥胖小鼠心脏功能损伤。为验证这一假说，我们采用高脂饮食诱导的肥胖小鼠模型、过表达miR-208小鼠模型、miR-208基因敲除小鼠模型及原代小鼠心肌细胞，在整体、组织及细胞水平，利用分子生物学技术，探讨miR-208是否通过抑制IRS2/PI3K/Akt通路介导高脂饮食诱导的肥胖小鼠心脏功能损伤。因此，本课题是我们前期研究的拓展和深入，是对肥胖患者心脏功能损伤机制及防治策略的进一步探讨，具有重要意义。

Obesity is one of the most important causes of heart dysfuction, but the mechanism remains unstated. MicroRNAs have been found to play an important role in heart development and cardiovascular disease in recent years. And the miRNA- 208 is highly expressed in myocardial tissue. Our previous study found that the myocardial function is damaged in obese mice induced by a high-fat diet, with the increased miRNA- 208 and decreased IRS2.However, the role and molecular mechanism of miR-208 on cardiac function in obese mice induced by high-fat diet remain unclear. Therefore, we propose a hypothesis: the abnormal cardiac function in obese mice induced by high-fat diet is closely related with miRNA-208 and its downstream IRS2 / PI3K/Akt pathway. To test this hypothesis, we will through the models including obese mice induced by high-fat diet, the overexpressed miR-208 mice, the miR-208(-/-) mice, and primary myocardial cells, from the overall level of the molecules, cells, tissues and animals aspects to discuss the role and mechanism of the miRNA-208 on cardiac function in obese mice induced by high-fat diet. Therefore, this study is the enlarging and deepening of our previous studies. It is further explore the mechanism of cardiac dysfunction and prevention in patients with obesity, and it has a very important significance.