Zhang Lin, Du Fu Hua, Kun Kai Xiao, Yan Yong
Department of Gastroenterology, Mianyang 404 Hospital, Sichuan, 621000, China.
Sichuan Science City Hospital, Sichuan, 621022, China.
Biochem Biophys Res Commun. 2025 Feb 2;747:151291. doi: 10.1016/j.bbrc.2025.151291. Epub 2025 Jan 6.
Non-alcoholic fatty liver disease (NAFLD) has emerged as a global health concern, placing a substantial financial strain on public health systems. Currently, no specific pharmacological treatments are recommended in existing guidelines. Abscisic acid (ABA), a natural plant hormone, is recognized for its promising potential in the healthcare field due to its diverse biological activities. Therefore, this study is aimed at exploring the protective mechanism of ABA against NAFLD. In vitro, experiments were conducted using palmitic acid (PA) to establish a fatty liver cell model, whereas in vivo, an NAFLD model was established using a continuous high-fat diet (HFD). It was found that ABA, as a natural activator of NRF2 and AMPK, reduced lipid accumulation in hepatocytes and exerted anti-inflammatory and antioxidant effects by enhancing the nuclear expression of NRF2, thereby alleviating NAFLD in mice. Furthermore, AMPK was activated by ABA through the promotion of its phosphorylation, which subsequently enhanced the p62-dependent autophagic degradation of KEAP1, leading to the release and nuclear translocation of NRF2. In conclusion, it is indicated that ABA reduces lipid accumulation, inflammation, and oxidative stress in hepatocytes via the NRF2 and AMPK pathways, potentially serving as a promising candidate for alleviating NAFLD.
非酒精性脂肪性肝病（NAFLD）已成为一个全球关注的健康问题，给公共卫生系统带来了巨大的经济压力。目前，现有指南中未推荐任何特定的药物治疗方法。脱落酸（ABA）是一种天然植物激素，因其多样的生物活性而在医疗保健领域具有广阔的潜在应用前景。因此，本研究旨在探索ABA对NAFLD的保护机制。在体外，使用棕榈酸（PA）建立脂肪肝细胞模型进行实验，而在体内，则使用持续高脂饮食（HFD）建立NAFLD模型。研究发现，ABA作为NRF2和AMPK的天然激活剂，可减少肝细胞内的脂质积累，并通过增强NRF2的核表达发挥抗炎和抗氧化作用，从而减轻小鼠的NAFLD。此外，ABA通过促进AMPK的磷酸化来激活它，随后增强KEAP1的p62依赖性自噬降解，导致NRF2的释放和核转位。总之，研究表明ABA通过NRF2和AMPK途径减少肝细胞内的脂质积累、炎症和氧化应激，有望成为缓解NAFLD的候选药物。
