Cidea promotes hepatic steatosis by sensing dietary fatty acids
Cidea promotes hepatic steatosis by sensing dietary fatty acids
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Cidea 通过感知膳食脂肪酸促进肝脏脂肪变性
DOI：
10.1002/hep.25611
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发表时间：
2012-07-01
期刊：
影响因子：
13.5
通讯作者：
Li, Peng
中科院分区：
文献类型：
--
作者：
Zhou, Linkang;Xu, Li;Li, Peng
高水平的饮食饱和脂肪与肝脂肪变性的发展密切相关，但介导这一过程的因素仍然难以捉摸。在这里，我们观察到细胞死亡诱导DNA片段化因子-α样效应子α（Cidea）的表达水平与人类肝脏脂肪变性的严重程度高度相关。Cidea在小鼠肝脏中的过表达导致肝脏脂质积聚增加和大脂滴（LDs）的形成。相比之下，Cidea缺乏的小鼠在接受高脂肪饮食喂养或ob/ob小鼠时，脂质积聚减少，肝脏脂肪变性减轻。此外，Cidea在ob/ob小鼠肝脏中的敲低导致肝脏脂质积累显著减少和LD较小。重要的是，我们观察到Cidea在肝细胞中的表达是由饱和脂肪酸（FA）特异性诱导的，当固醇反应元件结合蛋白（SREBP）1c被敲低时，这种诱导作用会降低。相反，SREBP 1c的过表达恢复了饱和的FA诱导的Cidea表达。此外，我们观察到Cidea蛋白在肝细胞中的稳定性在响应于用FA处理时显著增加。结论：Cidea通过作为对含有脂肪酸的饮食作出反应的传感器，在促进肝脏脂质蓄积和肝脂肪变性的发展中起关键作用。（肝病学2012;56：95107）
High levels of dietary saturated fat have been closely associated with the development of hepatic steatosis, but the factors that mediate this process remain elusive. Here, we observed that the level of cell death-inducing DNA fragmentation factor-alpha-like effector a (Cidea) expression was highly correlated with the severity of hepatic steatosis in humans. Overexpression of Cidea in mouse liver resulted in increased hepatic lipid accumulation and the formation of large lipid droplets (LDs). In contrast, mice with a Cidea deficiency had decreased lipid accumulation and alleviated hepatic steatosis when they received a high-fat-diet feeding or in ob/ob mice. Furthermore, the knockdown of Cidea in livers of ob/ob mice resulted in significantly reduced hepatic lipid accumulation and smaller LDs. Importantly, we observed that Cidea expression in hepatocytes was specifically induced by saturated fatty acids (FAs), and such induction was reduced when sterol response element-binding protein (SREBP)1c was knocked down. In contrast, the overexpression of SREBP1c restored the saturated FA-induced expression of Cidea. In addition, we observed that the stability of Cidea protein in hepatocytes increased significantly in response to treatment with FAs. Conclusion: Cidea plays critical roles in promoting hepatic lipid accumulation and in the development of hepatic steatosis by acting as a sensor that responds to diets that contain FAs. (Hepatology 2012;56:95107)