脂肪变性
脂质代谢
非酒精性脂肪肝
脂肪肝
内科学
组织病理学
β氧化
药理学
内分泌学
载脂蛋白E
生物
新陈代谢
化学
医学
疾病
病理
作者
Jiannan Qiu,Yifei Le,Lei Zhu,Lin Chen,Yuwei Jiang,Yizhen Wang,Xiaohui Fan,Xianglu Rong,Zhi‐Ling Yu,Songtao Li,Xiaobing Dou
标识
DOI:10.1021/acs.jafc.4c04929
摘要
Nonalcoholic fatty liver disease (NAFLD) causes significant global mortality and healthcare costs with no recommended pharmacological intervention for clinical management. Nuciferine (Nuc) is an alkaloid with aromatic rings, abundantly found in Nelumbo nucifera Gaertn. In this study, we explored the protective mechanisms of Nuc against hepatic steatosis and ferroptosis in NAFLD. High-fat diet (HFD) and healthy male ApoE–/– mice were used to induce NAFLD and a hypercholesterolemia model. Nuc was administered to the mice for four consecutive weeks from the ninth week. Various assessments, including histopathology, RNA sequencing, lipid metabolism, and ferroptosis-related protein expression, showed that Nuc alleviated hepatic steatosis and ferroptosis. We further showed that Nuc improves fatty acid accumulation and ferroptosis through the PPARα signaling pathway in mice and RSL3-treated AML-12 cells. The PPARα inhibitor GW6471 blocked Nuc's protective effects, leading to excess accumulation of iron ions. Thus, Nuc may be a potential therapeutic agent for NAFLD.
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