Glycyrrhizin ameliorates high fat diet-induced obesity in rats by activating NrF2 pathway
Glycyrrhizin ameliorates high fat diet-induced obesity in rats by activating NrF2 pathway
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DOI：
10.1016/j.lfs.2017.11.005
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发表时间：
2018-01-15
期刊：
影响因子：
6.1
通讯作者：
El-Shishtawy, Mamdouh M.
中科院分区：
文献类型：
--
作者：
El-Magd, Nada F. Abo;El-Mesery, Mohamed;El-Shishtawy, Mamdouh M.
目的：胰岛素抵抗性肥胖是一种慢性氧化应激和炎症状态，通过核因子红细胞2相关因子2（NrF 2）途径高度调节。预防性造模10周，随机分为正常组、GL组、HFD组和HFD+ GL组，每组10只，GL组在普通颗粒饲料基础上沿着口服甘草酸50 mg/kg/d，HFD组在HFD基础上沿着口服甘草酸。实验模型建立14周后，将大鼠分为正常组、HFD组和HFD+ GL组（从第10周开始给予甘草甜素）。主要结果：甘草甜素可显著降低大鼠体重和胰岛素抵抗，使脂质谱正常化，并显著减少脂肪组织中脂肪细胞的大小和肝组织中的脂质沉积。此外，葛根素还能显著降低肥胖大鼠肝脏丙二醛水平（P < 0.001），提高总抗氧化能力（P <0.001），从而改善肥胖大鼠的氧化应激。有趣的是，研究人员探讨了Escherin的分子机制，包括显著降低肝脏致炎酶mRNA表达肝脏胰岛素受体、NrF 2和同型加氧酶-1mRNA表达显著增加（P < 0.001）（P < 0.001），肝组织中NrF 2表达显著增加，并发生核转位。甘草甜素改善HFD诱导的大鼠肥胖，这可能归因于其增加胰岛素受体表达并激活NrF 2和随后的同型加氧酶-1途径的能力。因此，这项工作代表了一种安全的天然化合物（Escherin），它在预防或治疗肥胖相关的胰岛素抵抗方面具有重要作用。
Aim: Obesity based on insulin resistance is a state of chronic oxidative stress and inflammation that are highly regulated through nuclear factor Erythroid 2-related factor 2 (NrF2) pathway.Materials and methods: 70 male Wistar rats were randomized into two models. The prophylactic model was 10 weeks and rats were grouped into: normal group, GL group (received glycyrrhizin 50 mg/kg/day orally along with normal pellet diet), HFD group and HFD+ GL group (received glycyrrhizin along with HFD). The treatment model was 14 weeks and rats were grouped into: normal group, HFD group and HFD+ GL group (received glycyrrhizin from the week 10).Key findings: Glycyrrhizin decreased significantly rat weights and insulin resistance, normalized lipid profile and reduced significantly the adipocytes size in adipose tissue and lipid deposition in the liver tissue through histopathologic examination. Furthermore, glycyrrhizin ameliorated obesity-induced oxidative stress which indicated by significant decrease in liver malondialdehyde level (P < 0.001) and increase in the total antioxidant capacity (P < 0.001). Interestingly, molecular mechanism of glycyrrhizin was explored, that included significant reduction of liver gluconeogenic enzymes mRNA expression (P < 0.001), a significant increase of liver insulin receptor, NrF2 and homooxygenase-1 mRNA expressions (P < 0.001) and significant increase and nuclear translocation of NrF2 in liver tissue.Significance: Glycyrrhizin ameliorates HFD-induced obesity in rats that may be attributed to its ability to increase insulin receptor expression and to activate NrF2 and subsequent homooxygenase-1 pathway. Thus, this work represents a safe natural compound (glycyrrhizin) that has a great role either as prophylaxis or treatment for insulin resistance related to obesity.