Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 470, Issue -, Pages 160-167Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2017.10.010
Keywords
Lysosome associated membrane protein 3; Liver; Lipid metabolism; Triglycerides
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Funding
- National Natural Science Foundation of China [81700757, 81471039, 81401601]
- National Key R&D Program of China [2016YFC1101100]
- Natural Science Foundation Project of Chongqing [cstc2014jcyjjq10006, cstc2016jcyjA0093]
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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.
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