Li Meng, Chen Dahua, Huang Haixiu, Wang Jiewei, Wan Xingyong, Xu Chengfu, Li Chunxiao, Ma Han, Yu Chaohui, Li Youming
Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
PLoS One. 2017 Jun 1;12(6):e0178748. doi: 10.1371/journal.pone.0178748. eCollection 2017.
Caveolin1 (CAV1) is involved in lipid homeostasis and endocytosis, but little is known about the significance of CAV1 in the pathogenesis and development of nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the role of CAV1 in NAFLD.
Expression of CAV1 in the in vitro and in vivo models of NAFLD was analyzed. The effects of CAV1 knockdown or overexpression on free fatty acid (FFA)-induced lipid accumulation in L02 cells and AML12 cells were determined. CAV1 knockout (CAV1-KO) mice and their wild-type (WT) littermates were subjected to a high fat diet (HFD) for 4 weeks, and the functional consequences of losing the CAV1 gene and its subsequent molecular mechanisms were also examined.
Noticeably, CAV1 expression was markedly reduced in NAFLD. CAV1 knockdown led to the aggravation of steatosis that was induced by FFA in both L02 cells and AML12 cells, while CAV1 overexpression markedly attenuated lipid accumulation in the cells. Consistent with CAV1 repression in the livers of HFD-induced mice, the CAV1-KO mice exhibited more severe hepatic steatosis upon HFD intake. In addition, increased cholesterol levels and elevated transaminases were detected in the plasma of CAV1-KO mice. The protein expression of SREBP1, a key gene involved in lipogenesis, was augmented following CAV1 suppression in FFA-treated hepatocytes and in the livers of HFD-fed CAV1-KO mice.
CAV1 serves as an important protective factor in the development of NAFLD by modulating lipid metabolism gene expression.
小窝蛋白1（CAV1）参与脂质稳态和内吞作用，但关于CAV1在非酒精性脂肪性肝病（NAFLD）发病机制和发展中的意义知之甚少。本研究旨在确定CAV1在NAFLD中的作用。
分析了NAFLD体外和体内模型中CAV1的表达。确定了CAV1基因敲低或过表达对游离脂肪酸（FFA）诱导的L02细胞和AML12细胞脂质积累的影响。对CAV1基因敲除（CAV1-KO）小鼠及其野生型（WT）同窝小鼠进行4周高脂饮食（HFD）喂养，并研究缺失CAV1基因的功能后果及其后续分子机制。
值得注意的是，NAFLD中CAV1表达明显降低。CAV1基因敲低导致L02细胞和AML12细胞中FFA诱导的脂肪变性加重，而CAV1过表达则明显减轻细胞内脂质积累。与HFD诱导小鼠肝脏中CAV1表达受抑制一致，CAV1-KO小鼠在摄入HFD后表现出更严重的肝脂肪变性。此外，在CAV1-KO小鼠血浆中检测到胆固醇水平升高和转氨酶升高。在FFA处理的肝细胞和HFD喂养的CAV1-KO小鼠肝脏中，CAV1受抑制后，参与脂肪生成的关键基因SREBP1的蛋白表达增加。
CAV1通过调节脂质代谢基因表达，在NAFLD的发展中起重要保护作用。
