Genistein has beneficial effects on hepatic steatosis in high fat-high sucrose diet-treated rats
Genistein has beneficial effects on hepatic steatosis in high fat-high sucrose diet-treated rats
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DOI：
10.1016/j.biopha.2017.04.130
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发表时间：
2017-07-01
影响因子：
7.5
通讯作者：
Jiang, Zhuoqin
中科院分区：
文献类型：
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作者：
Liu, Huanhuan;Zhong, Huijia;Jiang, Zhuoqin
染料木黄酮是一种植物雌激素，在大豆中含量丰富，对减轻非酒精性脂肪性肝病（NAFLD）有一定作用，但其具体机制尚不清楚。本研究旨在探讨染料木黄酮对非酒精性脂肪肝的治疗作用及其可能的机制。雄性SD大鼠36只，随机分为4组：对照组、高脂高糖饮食组、高脂高糖饮食+4 mg/kg金雀异黄素组和高脂高糖饮食+8 mg/kg金雀异黄素组。12周后，观察血清和肝脏脂质谱，肝脏组织病理学检查。Western blot法检测肝脏AMP活化蛋白激酶（AMPK）、磷酸化AMPK（p-AMPK）、乙酰辅酶A羧化酶（ACC）、磷酸化ACC（p-ACC）和固醇调节元件结合蛋白1（SREBP-1）的蛋白水平。逆转录聚合酶链反应（RT-PCR）检测脂肪酸合成酶基因（FAS）、甘油-3-磷酸酰基转移酶（GPAT）、过氧化物酶体增殖物激活受体α（PPARa）、肉毒碱棕榈酰转移酶-1（CPT-1）和酰基辅酶A氧化酶（ACO）的mRNA表达。结果表明，染料木黄酮有效改善血清和肝脏脂质代谢，减少肝脏脂肪堆积。Genistein可使肝组织p-AMPK和p-ACC蛋白水平升高，而SREBP-1蛋白水平降低。与HFS组相比，Genistein组FAS、GPAT mRNA水平降低，PPARa、CPT-1、ACO mRNA水平升高。染料木黄酮可通过激活AMPK，促进脂肪酸氧化，抑制肝脏脂质合成，从而改善肝脏脂肪变性。(C)2017 Elsevier Masson SAS。All rights reserved.
Genistein, a kind of phytoestrogen abundant in soybeans, is beneficial for alleviating non-alcoholic fatty liver disease (NAFLD), but the specific mechanism was not clearly understood. This study was designed to determine the effect of genistein on NAFLD and explore the possible mechanism. 36 male Sprague-Dawley rats were divided into 4 groups: the control group, high fat-high sucrose diet (HFS) group, HFS with 4 mg/kg body weight genistein, and HFS with 8 mg/kg body weight genistein. 12 weeks later, serum and hepatic lipid profiles, liver histopathological examination were characterized. The protein levels of liver AMP-activated protein kinase (AMPK), phosphorylation of AMPK (p-AMPK), acetyl-CoA carboxylase (ACC), phosphorylation of ACC (p-ACC) and sterol regulatory element binding protein 1 (SREBP-1) were determined by western blot. mRNA expressions of fatty acid synthase gene (FAS) and glycerol-3-phosphate acyltransferase (GPAT), peroxisome proliferator-activated receptor a (PPARa), carnitine palmitoyl transfer enzyme-1 (CPT-1) and acyl-CoA oxidase (ACO) were measured by reverse transcription polymerase chain reaction (RT-PCR). Results showed that genistein effectively improved serum and hepatic lipid metabolism and diminished fat accumulation in liver. And the protein level of hepatic p-AMPK and p-ACC were increased, but SREBP-1 was decreased by genistein. Meanwhile, the mRNA levels of FAS and GPAT were lower, but PPARa, CPT-1, ACO were higher in rats treated with genistein compared with HFS group. Collectively, genistein can improve hepatic steatosis via activating AMPK, thus promoting fatty acid oxidation and inhibiting lipid synthesis in liver. (C) 2017 Elsevier Masson SAS. All rights reserved.