脂毒性
神经酰胺
脂肪肝
脂肪性肝炎
肝硬化
酒精性肝病
肝病
脂肪变性
肝细胞
胰岛素抵抗
癌症研究
生物
医学
内科学
疾病
内分泌学
细胞凋亡
生物化学
糖尿病
体外
作者
Xiaodong Yu,Jiong‐Wei Wang
标识
DOI:10.1016/j.bcp.2022.115157
摘要
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and its advanced form non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. Ceramides have been shown to exacerbate NAFLD development through enhancing insulin resistance, reactive oxygen species production, liver steatosis, lipotoxicity and hepatocyte apoptosis, and eventually causing hepatic inflammation and fibrosis. Emerging evidence indicates that ceramide production in NAFLD is predominantly attributed to activation of the de novo synthesis pathway of ceramides in hepatocytes. More importantly, pharmacological modulation of ceramide de novo synthesis in preclinical studies seems efficacious for the treatment of NAFLD. In this review, we provide an overview of the pathogenic mechanisms of ceramides in NAFLD, discuss recent advances and challenges in pharmacological interventions targeting ceramide de novo synthesis, and propose some research directions in the field.
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