Taurine Prevents High-Fat Diet-Induced-Hepatic Steatosis In Rats By Direct Inhibition Of Hepatic Sterol Regulatory Element-Binding Proteins And Activation Of Ampk

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY(2021)

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摘要
This study investigated if the protective effect of taurine against high fat diet-induced hepatic steatosis involves modulating the hepatic activity of 5' AMP-activated protein kinase (AMPK) and levels/activity of the sterol regulatory element-binding proteins-1/2 (SREBP1/2). Rats were divided into four groups (n = 12/group) as (a) STD, fed standard diet (3.85 kcal/g); (b) STD + taurine (500 mg/kg); (c) HFD, fed HFD (4.73 kcal/g); and (d) HFD + taurine. All treatments were conducted for 12 weeks. Independent of food intake or modulating glucose or insulin levels, taurine administration to STD and HFD-fed rats significantly lowered weekly weight gain and the accumulation of the retroperitoneal, visceral and subcutaneous fats. In both groups, taurine also reduced serum and hepatic levels of triglycerides and cholesterol and reduced hepatic mRNA and protein levels of fatty acid synthase (FAS), acetyl CoA carboxylase-1 (ACC-1), HMG-CoA-reductase and HMG-CoA synthetase. In control rats only, taurine reduced hepatic levels of mature forms of sterol regulatory element-binding proteins (SREBP)-1/2. In HFD-fed rats, taurine reduced SREBP-1/2 precursor and mature forms in the livers of HFD-fed rats. Besides, taurine significantly increased levels of glutathione (GSH), the activity of superoxide dismutase (SOD), and the activity of AMPK and its downstream beta-oxidation genes including peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and carnitine palmitoyltransferase (CPT-1) in the livers of both the control and HFD-fed rats. In conclusion, taurine protects against HFD-induced hepatic steatosis stimulating antioxidant levels, and concomitant stimulating hepatic beta-oxidation and suppressing lipid synthesis, mediated by activation of AMPK and suppression of SREBP-1.
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AMPK, hepatic steatosis, HFD, rats, SREBPs, taurine
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