Exogenous galanin alleviates hepatic steatosis by promoting autophagy via the AMPK-mTOR pathway

被引:2
作者
Zhu, Shuyuan [1 ]
Wang, Shuai [1 ]
Luo, Tao [1 ]
机构
[1] Chongqing Med Univ, Dept Geriatr, Affiliated Hosp 1, Chongqing 400016, Peoples R China
关键词
NAFLD; AMPK; & beta; -Oxidation; Autophagy; Galanin; FATTY LIVER-DISEASE; INSULIN-RESISTANCE; FOOD-INTAKE; PEPTIDE; ALPHA; ACTIVATION; HEALTH; GENE;
D O I
10.1016/j.abb.2023.109689
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Defective autophagy-induced intracellular lipid degradation is causally associated with non-alcoholic fatty liver disease (NAFLD) development. Therefore, agents that can restore autophagy may have potential clinical application prospects on this public health issue. Galanin (GAL) is a pleiotropic peptide that regulates autophagy and is a potential drug for the treatment of NAFLD. In this study, we used an MCD-induced NAFLD mouse model in vivo and an FFA-induced HepG2 hepatocyte model in vitro to evaluate the anti-NAFLD effect of GAL. Exogenous GAL supplementation significantly attenuated lipid droplet accumulation and suppressed hepatocyte TG levels in mice and cell models. Mechanistically, Galanin-mediated reduction of lipid accumulation was positively correlated with upregulated p-AMPK, as evidenced by upregulated protein expressions of fatty acid oxidation-related gene markers (PPAR-a and CPT1A), upregulated expressions of the autophagy-related marker (LC3B), and downregulated autophagic substrate p62 levels. In FFA-treated HepG2 cells, activation of fatty acid oxidation and autophagy-related proteins by galanin was reversed by autophagy inhibitors, chloroquine, and the AMPK inhibitor. Galanin ameliorates hepatic fat accumulation by inducing autophagy and fatty acid oxidation via the AMPK/mTOR pathway.
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页数:10
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