Department of Endocrinology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Department of Endocrinology, Xinqiao Hospital, Third Military Medical University, Chongqing, China; Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Mol Cell Endocrinol. 2018 Jul 15;470:160-167. doi: 10.1016/j.mce.2017.10.010. Epub 2017 Oct 19.
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.
溶酶体相关膜蛋白 3（LAMP3）是一种高度糖基化的蛋白质，是 LAMPs 家族的一员。LAMPs 家族在自噬溶酶体融合过程中发挥着关键作用。自噬最近被证实可以调节肝脂解。然而，LAMP3 在脂质代谢中的生理功能尚不清楚。在本研究中，我们发现非酒精性脂肪性肝病（NAFLD）患者和高脂肪饮食及 ob/ob 小鼠的肝组织中 LAMP3 的表达水平高于匹配对照组。游离脂肪酸处理的肝癌（HCC）细胞中 LAMP3 的表达也明显增加。此外，在 HCC 细胞中转染 LAMP3 后观察到细胞内脂滴和甘油三酯（TG）明显积累。进一步研究表明，LAMP3 过表达激活了 Akt 并上调了 HepG2 细胞中脂肪酸合成酶（FASN）和硬脂酰辅酶 A 去饱和酶 1（SCD-1）的表达。此外，用 PI3K/Akt 通路抑制剂处理可减弱 LAMP3 过表达引起的 TG 含量增加。我们的研究结果表明，LAMP3 是肝脏脂质代谢的重要调节因子，为将 LAMP3 作为脂质代谢紊乱相关疾病（如非酒精性脂肪性肝病和肥胖症）的药物靶点提供了依据。
