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首页> 外文期刊>The Journal of Nutritional Biochemistry >Combination of metformin and genistein alleviates non-alcoholic fatty liver disease in high -fat diet-fed mice
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Combination of metformin and genistein alleviates non-alcoholic fatty liver disease in high -fat diet-fed mice

机译：二甲双胍和尼斯坦的组合减轻了高饮食喂食小鼠的非酒精脂肪肝病

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摘要

Metformin (MET) and genistein (GEN) have a beneficial role in alleviating non-alcoholic fatty liver disease (NAFLD), but their combined effect on this disease has not yet been studied. The present study aimed to investigate the potential protective effects of combined MET and GEN on NAFLD in high-fat diet (HFD) fed mice. C57BL/6 male mice were fed on an HFD for 10 weeks. Animals were then divided into different groups and treated with MET (0.23%), GEN (0.2%) and MET +GEN (0.23% + 0.2%) for 3 months. Treatment with MET and GEN, alone or in combination significantly lowered body and liver weights and fasting blood glucose (FBG) in HFD mice. Combination therapy reduced liver triglyceride (TG) level and this effect was correlated with increased expression of carnitine palmitoyl transferase 1 (CPT1) gene, and reduced expression of fatty-acid synthase (FAS)and sterol regulatory element-binding protein-1c (SREBP-1c) genes. Combination therapy also affects gluconeogenesis pathway through decreasing expression of Glucose 6-phosphatase (G6Pase) and increasing phosphorylation of Glycogen synthase kinase 3 beta (GSK-3 beta). Furthermore, combination of MET and GEN ameliorates liver inflammation by switching macrophage into M2 phenotype, decreasing macrophage infiltration, reducing expression of pro-inflammatory cytokines and decreasing nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) activity. In addition, combination therapy enhances phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK). Taken together, these findings suggest that the combination of MET and GEN have beneficial effects against NAFLD in HFD-fed model. (C) 2020 Published by Elsevier Inc.
机译：二甲双胍（MET）和金雀异黄素（GEN）在缓解非酒精性脂肪肝（NAFLD）方面具有有益作用，但它们对该疾病的联合作用尚未得到研究。本研究旨在研究高脂饮食（HFD）喂养的小鼠中MET和GEN联合应用对NAFLD的潜在保护作用。将C57BL/6雄性小鼠喂食HFD 10周。然后将动物分为不同的组，分别用MET（0.23%）、GEN（0.2%）和MET+GEN（0.23%+0.2%）治疗3个月。MET和GEN单独或联合治疗可显著降低HFD小鼠的体重、肝脏重量和空腹血糖（FBG）。联合治疗降低了肝脏甘油三酯（TG）水平，这种效应与肉碱棕榈酰转移酶1（CPT1）基因表达增加、脂肪酸合成酶（FAS）和甾醇调节元件结合蛋白-1c（SREBP-1c）基因表达减少有关。联合治疗还通过降低葡萄糖6-磷酸酶（G6Pase）的表达和增加糖原合成酶激酶3β（GSK-3β）的磷酸化来影响糖异生途径。此外，MET和GEN联合使用可通过将巨噬细胞转化为M2表型、减少巨噬细胞浸润、减少促炎细胞因子的表达以及降低活化B细胞的核因子-κ轻链增强子（NF-κB）活性来改善肝脏炎症。此外，联合治疗可增强5'腺苷一磷酸活化蛋白激酶（AMPK）的磷酸化。综上所述，这些研究结果表明，在HFD喂养模型中，MET和GEN的联合使用对NAFLD具有有益的作用。（C） 2020年由爱思唯尔公司出版。

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