YAP甲基化修饰促进肥胖发生的机制研究

Mechanism of YAP Methylation Promoting Obesity

肥胖引起的并发症日益增多,严重影响人们的生理心理健康。该研究发现,YAP甲基化可以调节脂肪酸合成氧化促进肥胖的发生。使用Yap K327M(YAP第327位赖氨酸发生单甲基化修饰)转基因小鼠证明YAP甲基化修饰与肥胖表型的关系;采用qRT-PCR检测方法分析YAP甲基化对脂肪酸合成和氧化过程中关键基因表达水平的影响;运用小鼠在体葡萄糖和生长因子耐受实验对Yap K327M转基因肥胖小鼠在体葡萄糖及生长因子水平进行检测以及对临床样品进行免疫组织化学分析。结果显示,YAP甲基化通过促进脂肪酸合成和抑制脂肪酸氧化,抑制葡萄糖和生长因子耐受,进而导致小鼠肥胖发生,并且肥胖病人脂肪组织中YAP甲基化水平显著提高。以上研究提示,YAP甲基化可能是临床肥胖诊断及预防的潜在标志物。

The increasing number of complications caused by obesity has a serious impact on people’s physical and mental health.The study found that YAP methylation could regulate fatty acid synthesis and oxidation to promote obesity.Yap K327M transgenic mice were used to demonstrate the relationship between YAP methylation and obesity,qRT-PCR was used to analyze the effect of YAP methylation on the expression of key genes in fatty acid synthesis and oxidation.The levels of glucose and growth factor in Yap K327M transgenic mice were analyzed by in vivo glucose and growth factor tolerance test,and the clinical samples were analyzed by immunohistochemical method.Data showed that YAP methylation promoted fatty acid synthesis and inhibited fatty acid oxidation.It can also suppressed glucose and growth factor tolerance,and then led to obesity in mice.Moreover,the level of YAP methylation in adipose tissue was significantly increased in obese patients.These results suggest that YAP methylation may be a potential marker for the diagnosis and prevention of obesity.