CD36 plays a negative role in the regulation of lipophagy in hepatocytes through an AMPK-dependent pathway[S]
CD36 plays a negative role in the regulation of lipophagy in hepatocytes through an AMPK-dependent pathway[S]
复制标题
CD36 通过 AMPK 依赖性途径在肝细胞自噬调节中发挥负面作用。
DOI：
10.1194/jlr.m090969
复制
发表时间：
2019-04-01
影响因子：
6.5
通讯作者：
Ruan, Xiong Z.
中科院分区：
文献类型：
--
作者：
Li, Yun;Yang, Ping;Ruan, Xiong Z.
脂肪酸转位酶簇分化（CD36）是一种促进长链脂肪酸摄取的多功能膜蛋白。脂噬是脂滴的自噬降解。越来越多的证据表明，CD36参与调节脂肪酸储存或使用的细胞内信号转导的调节。然而，我们对CD36与脂噬之间的关系知之甚少。在这项研究中，我们发现在高脂肪饮食处理的小鼠肝脏中，CD36表达的增加伴随着自噬的减少。HepG2和Huh7细胞过表达CD36可抑制自噬，而敲低CD36表达可诱导自噬，这是由于自噬通量中自噬体形成增加。同时，敲除CD36小鼠的自噬增加，而敲除CD36小鼠的CD36表达重建则降低了自噬。HepG2细胞中CD36的敲低增加了脂质吞噬和β -氧化，这有助于改善脂质积累。此外，CD36的表达通过AMPK途径调控自噬，ULK1/Beclin1的磷酸化也参与了这一过程。这些发现表明CD36是自噬的负调节因子，通过改善CD36表达诱导脂噬可能是通过减轻脂质过度积累治疗脂肪肝疾病的潜在治疗策略。
Fatty acid translocase cluster of differentiation (CD36) is a multifunctional membrane protein that facilitates the uptake of long-chain fatty acids. Lipophagy is autophagic degradation of lipid droplets. Accumulating evidence suggests that CD36 is involved in the regulation of intracellular signal transduction that modulates fatty acid storage or usage. However, little is known about the relationship between CD36 and lipophagy. In this study, we found that increased CD36 expression was coupled with decreased autophagy in the livers of mice treated with a high-fat diet. Overexpressing CD36 in HepG2 and Huh7 cells inhibited autophagy, while knocking down CD36 expression induced autophagy due to the increased autophagosome formation in autophagic flux. Meanwhile, knockout of CD36 in mice increased autophagy, while the reconstruction of CD36 expression in CD36-knockout mice reduced autophagy. CD36 knockdown in HepG2 cells increased lipophagy and beta-oxidation, which contributed to improving lipid accumulation. In addition, CD36 expression regulated autophagy through the AMPK pathway, with phosphorylation of ULK1/Beclin1 also involved in the process. These findings suggest that CD36 is a negative regulator of autophagy, and the induction of lipophagy by ameliorating CD36 expression can be a potential therapeutic strategy for the treatment of fatty liver diseases through attenuating lipid overaccumulation.