Song Qi, Guo Jun Xia, Ma Yu Xun, Ou Tong, Zhang Jing, Li Hui Zi, Mi Sheng Quan, Zhang Yan Zhen, Oda Hiroaki, Chen Wen
Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing, 100191, China.
Laboratory of Nutritional Biochemistry, Nagoya University, Nagoya, 464-8601, Japan.
Heliyon. 2023 May 23;9(6):e16401. doi: 10.1016/j.heliyon.2023.e16401. eCollection 2023 Jun.
Taurine has been proven in many trials to alleviate the symptoms of metabolic associated fatty liver disease. Here its protective effect for hepatic steatosis and modulation of AMP-activated protein kinase and insulin signaling pathway were investigated. Steatotic HepG2 cell established with oleic acid (0.05 mmol/L), treated with taurine (5 mmol/L), dorsomorphin (10 μmol/L) for 24 h. Sprague Dawley rats were divided into regular and high-fat diet (HFD) groups, and their corresponding taurine (70 or 350 mg/kg BW/d) groups, fed for 8 weeks. In steatotic cell, taurine reduced the TG concentration and SREBP-1c, PPARγ, FAS, ACC, SCD1 protein levels, decreased phosphorylation of mTOR, IRS1 (Ser302), increased phosphorylation of AMPKα, LKB1, PI3K, Akt, ACC. While dorsomorphin eliminated taurine's TG-lowering effect. In HFD-fed rats, taurine reduced liver TG, serum TG, ALT, AST, IL-1β, IL-4, TNF-α. The effects of taurine on the main factors of fatty acid synthesis were mostly consistent with cell experiments, and the reduction of microRNAs (451, 33, 291b) was aligned with the improvement in LKB1 and AMPK expression in HFD rats. Taurine alleviated steatosis-induced inhibition of IRS1-PI3K-Akt pathway, but suppressed its positively regulated downstream factor mTOR. In parallel, taurine reduced steatosis by activating LKB1-AMPKα pathway via phosphorylation and no-phosphorylation manner, then inhibiting SREBP-1c directly or by suppressing mTOR phosphorylation.
在许多试验中已证实牛磺酸可减轻代谢相关脂肪性肝病的症状。在此,研究了其对肝脂肪变性的保护作用以及对AMP激活的蛋白激酶和胰岛素信号通路的调节作用。用油酸(0.05 mmol/L)建立脂肪变性的HepG2细胞,用牛磺酸(5 mmol/L)、 dorsomorphin(10 μmol/L)处理24小时。将Sprague Dawley大鼠分为正常饮食组和高脂饮食(HFD)组,以及相应的牛磺酸(70或350 mg/kg体重/天)组,喂养8周。在脂肪变性细胞中,牛磺酸降低了TG浓度以及SREBP-1c、PPARγ、FAS、ACC、SCD1蛋白水平,降低了mTOR、IRS1(Ser302)的磷酸化水平,增加了AMPKα、LKB1、PI3K、Akt、ACC的磷酸化水平。而dorsomorphin消除了牛磺酸降低TG的作用。在高脂饮食喂养的大鼠中,牛磺酸降低了肝脏TG、血清TG、ALT、AST、IL-1β、IL-4、TNF-α。牛磺酸对脂肪酸合成主要因子的影响大多与细胞实验一致,并且在高脂饮食大鼠中,微小RNA(451、33、291b)的减少与LKB1和AMPK表达的改善一致。牛磺酸减轻了脂肪变性诱导的IRS1-PI3K-Akt通路抑制,但抑制了其正向调节的下游因子mTOR。同时,牛磺酸通过磷酸化和非磷酸化方式激活LKB1-AMPKα通路,进而直接抑制SREBP-1c或通过抑制mTOR磷酸化来减轻脂肪变性。