Zhang Yuxuan, Zhou Jiali, Yang Lan, Xiao Hang, Liu Dongbo, Kang Xincong
Horticulture College, Hunan Agricultural University, Changsha 410128, China.
State Key Laboratory of Subhealth Intervention Technology, Hunan Agricultural University, Changsha 410128, China.
Antioxidants (Basel). 2024 Dec 9;13(12):1501. doi: 10.3390/antiox13121501.
Lipid accumulation and oxidative stress, which could be improved by autophagy, are the "hits" of metabolic-associated fatty liver disease (MAFLD). spore powder (GLSP) has the effect of improving liver function. However, there are few reports about its effects on and mechanisms impacting MAFLD alleviation. This study investigated the effect of GLSP on hepatic lipid accumulation and oxidative stress and explored the role that autophagy played in this effect. The results showed that GLSP effectively reduced lipid accumulation and activated autophagy in the livers of mice with high-fat-diet-induced disease and palmitic acid-induced hepatocytes. GLSP reduced the lipid accumulation by reducing lipogenesis and promoting lipid oxidation in HepG2 cells. It decreased the production of ROS, increased the activity of SOD and CAT, and improved the mitochondrial membrane potential via the Keap1/Nrf2 pathway. The alleviating effects of GLSP on the lipid accumulation and oxidative stress was reversed by 3-methyladenine (3-MA), an autophagy inhibitor. GLSP activated autophagy via the AMPK pathway in HepG2 cells. In conclusion, GLSP could attenuate MAFLD by the improvement of lipid accumulation and oxidative stress via autophagy. This paper is the first to report the improvement of MAFLD through autophagy promotion. It will shed novel light on the discovery of therapeutic strategies targeting autophagy for MAFLD.
脂质积累和氧化应激是代谢相关脂肪性肝病(MAFLD)的“致病因素”,而自噬可改善这两者。灵芝孢子粉(GLSP)具有改善肝功能的作用。然而,关于其对MAFLD缓解的影响及机制的报道较少。本研究调查了GLSP对肝脏脂质积累和氧化应激的影响,并探讨了自噬在其中所起的作用。结果表明,GLSP能有效减少高脂饮食诱导的小鼠肝脏和棕榈酸诱导的肝细胞中的脂质积累并激活自噬。GLSP通过减少HepG2细胞中的脂肪生成和促进脂质氧化来降低脂质积累。它通过Keap1/Nrf2途径减少活性氧的产生,增加超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性,并改善线粒体膜电位。自噬抑制剂3-甲基腺嘌呤(3-MA)可逆转GLSP对脂质积累和氧化应激的缓解作用。GLSP在HepG2细胞中通过AMPK途径激活自噬。总之,GLSP可通过自噬改善脂质积累和氧化应激来减轻MAFLD。本文首次报道了通过促进自噬改善MAFLD。这将为发现针对MAFLD的自噬治疗策略提供新的思路。