自噬
安普克
下调和上调
甘丙肽
β氧化
PI3K/AKT/mTOR通路
肝细胞
脂肪肝
化学
脂肪变性
AMP活化蛋白激酶
内分泌学
脂滴
内科学
细胞生物学
脂肪酸
生物
生物化学
蛋白激酶A
信号转导
磷酸化
医学
受体
体外
细胞凋亡
神经肽
疾病
基因
作者
Shuyuan Zhu,Shuai Wang,Tao Luo
标识
DOI:10.1016/j.abb.2023.109689
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-α 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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