eprintid: 10068746
rev_number: 39
eprint_status: archive
userid: 608
dir: disk0/10/06/87/46
datestamp: 2019-02-26 16:06:16
lastmod: 2021-09-26 22:38:02
status_changed: 2019-02-28 17:22:13
type: article
metadata_visibility: show
creators_name: Li, Y
creators_name: Yang, P
creators_name: Zhao, L
creators_name: Chen, Y
creators_name: Zhang, X
creators_name: Zeng, S
creators_name: Wei, L
creators_name: Varghese, Z
creators_name: Moorhead, JF
creators_name: Chen, Y
creators_name: Ruan, XZ
title: CD36 plays a negative role in the regulation of lipophagy in hepatocytes through an AMPK-dependent pathway
ispublished: inpress
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: G93
keywords: Beta-oxidation, CD36, Fatty acid/Oxidation, Hepatic steatosis, Lipid droplets, Liver, lipophagy
note: This version is the author accepted manuscript version. For information on re-use, please refer to the publisher’s terms and conditions.
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.
date: 2019
date_type: published
official_url: https://doi.org/10.1194/jlr.M090969
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1622010
doi: 10.1194/jlr.M090969
pii: jlr.M090969
lyricists_name: Ruan, Xiong-Zhong
lyricists_id: XZRUA13
actors_name: Nonhebel, Lucinda
actors_id: LNONH33
actors_role: owner
full_text_status: public
publication: Journal of Lipid Research
issn: 0022-2275
citation:        Li, Y;    Yang, P;    Zhao, L;    Chen, Y;    Zhang, X;    Zeng, S;    Wei, L;                 ... Ruan, XZ; + view all <#>        Li, Y;  Yang, P;  Zhao, L;  Chen, Y;  Zhang, X;  Zeng, S;  Wei, L;  Varghese, Z;  Moorhead, JF;  Chen, Y;  Ruan, XZ;   - view fewer <#>    (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 <https://doi.org/10.1194/jlr.M090969>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10068746/8/Ruan%20accepted%20version.pdf