Taurine Alleviated Hepatic Steatosis in Oleic Acid-Treated-HepG2 Cells and Rats Fed a High-Fat Diet

Background and objectives: Non-alcoholic fatty liver disease (NAFLD) is a widespread chronic liver disease defined predominantly by steatosis (triglyceride (TG) accumulation), but there is no approved pharmaceutical treatment. Taurine is an amino acid that has been proven in many trials to alleviate the symptoms of NAFLD. Here we investigated whether the protective effect of taurine against steatosis involves the modulating of AMP-activated protein kinase (AMPK) and insulin signaling pathway. Methods: The steatotic HepG2 cell model, established with 0.05mmol/L oleic acid, was treated with 5mmol/L taurine and/or 10μmol/L dorsomorphin for 24h. Sprague Dawley rats were divided into 6 groups: control group (regular diet), model group (high-fat diet), and their corresponding high/low dose taurine groups (70 and 350 mg/kg BW/d). All treatments were conducted for 8 weeks. Results: In steatotic HepG2 cell model, taurine significantly reduced the TG concentration and protein expressions of sterol regulatory element binding proteins-1c (SREBP-1c), peroxisome proliferators activated receptor γ (PPARγ), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), stearoyl-CoA desaturase1 (SCD1). With taurine supplementation, phosphorylation of mammalian target of rapamycin (mTOR), insulin receptor substrate 1 (IRS1) (Ser302) was decreased and phosphorylation of AMPKα, liver kinase B1 (LKB1), phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt), ACC was increased. However, the TG-lowering effect of taurine in steatotic HepG2 cells was eliminated by the supplement of AMPK inhibitor- dorsomorphin. In animal experiments, taurine reduced liver and serum TG, as well as serum ALT, AST, IL-1β, IL-4 and TNF-α in rats fed a high-fat diet. The effects of taurine on the main enzymes and regulatory factors in TG synthesis were consistent with most results in steatotic HepG2 cell experiments. Conclusions: Taurine alleviated the inhibition of IRS1-PI3K-Akt pathway caused by steatosis, and reduced hepatic steatosis by activating LKB1-AMPKα pathway, suppressing mTOR, SREBP-1c and PPARγ.