Taurine prevents high‐fat diet‐induced‐hepatic steatosis in rats by direct inhibition of hepatic sterol regulatory element‐binding proteins and activation of AMPK

牛磺酸 内科学 内分泌学 甾醇调节元件结合蛋白 脂肪变性 脂肪酸合酶 安普克 化学 肉碱 AMP活化蛋白激酶 过氧化物酶体 胆汁酸 蛋白激酶A 胆固醇 生物 甾醇 脂质代谢 生物化学 激酶 受体 氨基酸 医学
作者
Mohamed D Morsy,Moutasem Salih Aboonq,Mohammed Abadi ALsleem,Abdalla Abdelrahim Abusham
出处
期刊:Clinical and Experimental Pharmacology and Physiology [Wiley]
卷期号:48 (1): 72-85 被引量:19
标识
DOI:10.1111/1440-1681.13387
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 β-oxidation genes including peroxisome proliferator-activated receptor-α (PPAR-α) 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 β-oxidation and suppressing lipid synthesis, mediated by activation of AMPK and suppression of SREBP-1.

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