Inhibition of mGluR5 ameliorates lipid accumulation and inflammation in HepG2 cells

作者全名："Zeng, Shu; Tao, Min; Yuan, Lei; Zhang, Lili; Luo, Xie"

作者地址："[Zeng, Shu] Chongqing Med Univ, Ctr Lipid Res, Chongqing, Peoples R China; [Zeng, Shu] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Key Lab Mol Biol Infect Dis,Minist Educ,Dept Infec, Chongqing, Peoples R China; [Zeng, Shu] Third Mil Med Univ, Army Med Univ, Inst Digest Dis PLA, Cholestat Liver Dis Ctr,Dept Gastroenterol, Chongqing, Peoples R China; [Zeng, Shu] Third Mil Med Univ, Affiliated Hosp 1, Ctr Metab Associated Fatty Liver Dis, Southwest Hosp,Army Med Univ, Chongqing, Peoples R China; [Tao, Min; Yuan, Lei; Zhang, Lili; Luo, Xie] Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol, 74 Linjiang Rd, Chongqing 400010, Peoples R China"

通信作者："Luo, X (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol, 74 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000964829800001

JCR分区：Q2

影响因子：3.1

年份：2023

卷号：653

期号：　

开始页：1

结束页：11

文献类型：Article

关键词：Metabotropic glutamate receptor 5; Lipogenesis; Inflammation; JNK; Nonalcoholic fatty liver disease

摘要："Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease characterized by ectopic lipid accumulation in hepatocytes. To date, no specific drug has been approved for its treatment. Metabotropic glutamate receptor 5 (mGluR5) has been showed expressed in hepatocytes and related to some liver diseases such as alcoholic steatosis. However, the function of mGluR5 in NAFLD is not clear. This work aims to investigate the effect and potential mechanism of mGluR5 in NAFLD. We found that mGluR5 expression was increased in the livers of HFD-fed mice and in palmitate-treated HepG2 cells. Suppression of mGluR5 by the specific antagonist MPEP could ameliorate palmitate-induced lipid accumulation, whereas the mGluR5 agonist CHPG promoted lipid deposition in the cells. Knockdown of mGluR5 by small interfering RNA further demonstrated that inhibition of mGluR5 could reduce lipid accumulation. Furthermore, our results revealed that mGluR5 regulated lipid metabolism by increasing the gene expression of lipogenesis. Inflammatory factors and phosphorylation levels of NF-KB-p65 and JNK were also tested in treated hepatocytes. mGluR5 promoted the inflammatory reaction and JNK phosphorylation. Inhibition of JNK signaling by JNK-IN-8 rescued CHPG-induced lipogenesis and inflammation. This study showed mGluR5 regulated lipid accumulation and inflammation in palmitic acid-treated HepG2 cells via the JNK signaling pathway. mGluR5 might be a potential drug target for NAFLD.(c) 2023 Elsevier Inc. All rights reserved."

基金机构：National Natural Science Foundation of China [81800771]

基金资助正文：This study was supported by a grant from the National Natural Science Foundation of China (81800771) .