【摘 要】
：
代谢综合征为一种常见代谢性疾病,已构成全球性的健康问题.新近研究提示,Tribbles同源蛋白3 (TRB3)在调控糖尿病心肌病中发挥重要作用,提示TRB3可能介导机体代谢损伤.我们发现,高脂膳食诱导的小鼠代谢综合症导致肝脏、心脏、肾脏、肺脏中TRB3与自噬底物p62的水平增加,并且肝脏中TRB3与p62存在明显共定位.针对小鼠肝脏进行研究发现自噬上游信号通路活化,然而自噬底物p62以不可溶形态大
【出 处】
：
第一届自噬生物学与疾病国际研讨会(The 1st International Symposium on Autophag
论文部分内容阅读
代谢综合征为一种常见代谢性疾病,已构成全球性的健康问题.新近研究提示,Tribbles同源蛋白3 (TRB3)在调控糖尿病心肌病中发挥重要作用,提示TRB3可能介导机体代谢损伤.我们发现,高脂膳食诱导的小鼠代谢综合症导致肝脏、心脏、肾脏、肺脏中TRB3与自噬底物p62的水平增加,并且肝脏中TRB3与p62存在明显共定位.针对小鼠肝脏进行研究发现自噬上游信号通路活化,然而自噬底物p62以不可溶形态大量堆积,提示自噬流的阻断.游离脂肪酸(FFA)刺激的肝脏细胞系AML 12中同样可观察到TRB3与P62蛋白水平的增加及二者的共定位.在FFA刺激的AML 12细胞中加入TLR2、TLR4中和抗体可降低TRB3水平,下调炎症、细胞衰老反应.在FFA刺激的AML 12细胞中过表达TRB3可增加不可溶p62、炎症、ROS、细胞衰老与脂肪堆积水平,相反,使用TRB3 siRNA可显著改善以上病变水平.综上,本研究发现TRB3通过与p62相互作用抑制肝脏自噬降解功能,促进高脂膳食诱导的小鼠代谢综合征.
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