Icaritin ameliorates hepatic steatosis via promoting fatty acid β-oxidation and insulin sensitivity
Icaritin ameliorates hepatic steatosis via promoting fatty acid β-oxidation and insulin sensitivity
复制标题
淫羊藿素通过促进脂肪酸β-氧化和胰岛素敏感性改善肝脏脂肪变性
DOI：
10.1016/j.lfs.2020.119000
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发表时间：
2021-01-07
期刊：
影响因子：
6.1
通讯作者：
Li, Yinxiong
中科院分区：
文献类型：
--
作者：
Xiong, Yue;Chen, Yan;Li, Yinxiong
目的：研究淫羊藿苷(ICT)对高脂饮食(HFD)诱导的小鼠肝细胞脂肪毒性和脂肪变性的影响，并探讨其可能的作用机制。结果：体外研究表明，ICT主要通过增强线粒体呼吸、脂肪酸氧化和轻度减少脂肪酸的合成，对PA诱导的脂肪变性有明显的保护作用。高脂饲料喂养8周的小鼠模型表现出代谢紊乱，而ICT应用显著降低了体重、血糖水平、胰岛素抵抗、肝脏脂肪变性水平和脂肪含量。与细胞系中的观察结果一致，ICT通过提高过氧化体增殖物激活受体a(PPARα)的表达，挽救了HFD受损的与脂肪酸β氧化相关的关键因素的功能和含量。同时，还逆转了AKT和GSK3β的磷酸化水平下降，导致胰岛素抵抗的改善。意义：ICT对PA或HFD诱导的肝脏脂肪变性和代谢紊乱有治疗作用。这可能为构建肝脏脂肪变性的预防和治疗手段提供新的策略。
Aim: This study aimed to reveal the effects of icaritin (ICT) on lipotoxicity induced by palmitate (PA) in hepatic cells and steatosis in high-fat diet (HFD)-fed mice as well as exploring the potential mechanisms.Main methods: Primary mouse hepatocytes and human hepatoma Huh7 cells were used to evaluate ICT effect in vitro. HFD-fed mice were used to evaluate the ICT effect in vivo.Results: In vitro study indicated that ICT significantly rescued PA-induced steatosis, mainly through a combination of robust increased mitochondrial respiration, fatty acid oxidation and mildly decreased synthesis of fatty acid. An HFD-fed mouse model with 8 weeks HFD-fed showed metabolic disorders, while ICT application significantly reduced the weight, serum glucose levels, insulin resistance, hepatic steatosis level and adipose contents. In consistent with the observations in cell lines, ICT rescued the HFD-impaired functions and contents of key factors related to fatty acid beta-oxidation through elevated expression of peroxisome proliferator-activated receptor a (PPAR alpha). Meanwhile, it also reversed the decreased phosphoryl levels of AKT and glucogen synthase kinase 3 (GSK3 beta), leading to the improvement of insulin resistance.Significance: ICT administration had a therapeutic effect on PA- or HFD-induced hepatic steatosis and metabolic disorders. It may provide a novel strategy to construct preventive and therapeutic means for hepatic steatosis.