LAMP3 regulates hepatic lipid metabolism through activating PI3K/Akt pathway
LAMP3 regulates hepatic lipid metabolism through activating PI3K/Akt pathway
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LAMP3通过激活PI3K/Akt通路调节肝脏脂质代谢
DOI：
10.1016/j.mce.2017.10.010
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发表时间：
2018-07-15
影响因子：
4.1
通讯作者：
Zheng, Hongting
中科院分区：
文献类型：
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作者：
Liao, Xiaoyu;Song, Lingyu;Zheng, Hongting
溶酶体相关膜蛋白3（lysosomeassociatedmembraneprotein 3，LAMP 3）是一种高度糖基化的蛋白质，属于LAMP家族成员。LAMPs家族在自体溶酶体融合过程中起着关键作用。最近证实自噬调节肝脏脂肪分解。然而，LAMP 3在脂质代谢中的生理功能尚不清楚。在目前的研究中，我们发现LAMP 3在非酒精性脂肪肝病（NAFLD）患者和高脂饮食和ob/ob小鼠的肝组织中的表达水平高于匹配的对照组。游离脂肪酸处理的肝细胞癌（HCC）细胞中LAMP 3表达也明显增加。此外，在HCC细胞中过表达LAMP 3后观察到细胞内脂滴和甘油三酯（TG）的显著积累。进一步的研究表明，在HepG 2细胞中，LAMP 3过表达激活Akt并上调脂肪生成酶FXR和SCD-1的表达。此外，通过用PI 3 K/Akt通路抑制剂处理，LAMP 3过表达诱导的TG含量增加被减弱。我们的研究结果表明，LAMP 3是肝脏脂质代谢的重要调节因子，这为将LAMP 3作为脂质代谢紊乱相关疾病（如NAFLD和肥胖）的药物靶点提供了一系列证据。(C)2017爱思唯尔B. V.保留所有权利。
Lysosome associated membrane protein 3 (LAMP3), a highly glycosylated protein, is one member of the LAMPs family. LAMPs family plays a critical role in the autolysosome fusion process. Autophagy was recently confirmed to regulate hepatic lipolysis. However, the physiological function of LAMP3 in lipid metabolism is not clear. In the current study, we discovered that the LAMP3 expression level was higher in the liver tissues of non-alcoholic fatty liver disease (NAFLD) patients and high-fat diet and ob/ob mice than in the matched control groups. LAMP3 expression was also obviously increased in hepatocellular carcinoma (HCC) cells treated with free fatty acids. Moreover, marked accumulation of intracellular lipid droplets and triglycerides (TG) was observed after LAMP3 overexpression in HCC cells. Further study showed that LAMP3 overexpression activated Akt and upregulated the expression of the lipogenic enzymes FASN and SCD-1 in HepG2 cells. Additionally, the increased TG content induced by LAMP3 overexpression was attenuated by treatment with a PI3K/Akt pathway inhibitor. Our findings demonstrated that LAMP3 is an important regulator of hepatic lipid metabolism, which provides a line of evidence for taking LAMP3 as a drug target in lipid metabolism disorder-associated diseases, such as NAFLD and obesity. (C) 2017 Elsevier B.V. All rights reserved.