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CD36 plays a negative role in the regulation of lipophagy in hepatocytes through an AMPK-dependent pathway

Li, Y; Yang, P; Zhao, L; Chen, Y; Zhang, X; Zeng, S; Wei, L; ... Ruan, XZ; + view all (2019) CD36 plays a negative role in the regulation of lipophagy in hepatocytes through an AMPK-dependent pathway. Journal of Lipid Research 10.1194/jlr.M090969. (In press). Green open access

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Abstract

Fatty acid translocase CD36 (CD36) is a multifunctional membrane protein that facilitates the uptake of long-chain fatty acid (LCFA). 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 increasedCD36 expression was coupled with decreasedautophagy 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 reconstruction of CD36 expression in CD36-knockout mice reduced autophagy. CD36 knockdown in HepG2 cells increased lipophagy and β-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 induction of lipophagy by ameliorating CD36 expression can be a potential therapeutic strategy for the treatment of fatty liver diseases through attenuating lipid over-accumulation.

Type: Article
Title: CD36 plays a negative role in the regulation of lipophagy in hepatocytes through an AMPK-dependent pathway
Open access status: An open access version is available from UCL Discovery
DOI: 10.1194/jlr.M090969
Publisher version: https://doi.org/10.1194/jlr.M090969
Language: English
Additional information: This version is the author accepted manuscript version. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Beta-oxidation, CD36, Fatty acid/Oxidation, Hepatic steatosis, Lipid droplets, Liver, lipophagy
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10068746
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