Abo El-Magd Nada F, El-Mesery Mohamed, El-Karef Amro, El-Shishtawy Mamdouh M
Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
Life Sci. 2018 Jan 15;193:159-170. doi: 10.1016/j.lfs.2017.11.005. Epub 2017 Nov 10.
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.
70 male Wistar rats were randomized into two models. The prophylactic model was 10weeks and rats were grouped into: normal group, GL group (received glycyrrhizin 50mg/kg/day orally along with normal pellet diet), HFD group and HFD+ GL group (received glycyrrhizin along with HFD). The treatment model was 14weeks and rats were grouped into: normal group, HFD group and HFD+GL group (received glycyrrhizin from the week 10).
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.
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.
基于胰岛素抵抗的肥胖是一种慢性氧化应激和炎症状态，其通过核因子红细胞2相关因子2（NrF2）途径受到高度调节。
70只雄性Wistar大鼠被随机分为两种模型。预防模型为期10周，大鼠被分为：正常组、GL组（口服甘草酸50mg/kg/天，同时给予正常颗粒饲料）、高脂饮食（HFD）组和HFD + GL组（给予甘草酸及高脂饮食）。治疗模型为期14周，大鼠被分为：正常组、HFD组和HFD + GL组（从第10周开始给予甘草酸）。
通过组织病理学检查，甘草酸显著降低了大鼠体重和胰岛素抵抗，使血脂谱正常化，并显著减小了脂肪组织中的脂肪细胞大小以及肝脏组织中的脂质沉积。此外，甘草酸改善了肥胖诱导的氧化应激，这表现为肝脏丙二醛水平显著降低（P<0.001）以及总抗氧化能力增加（P<0.001）。有趣的是，对甘草酸的分子机制进行了探索，包括肝脏糖异生酶mRNA表达显著降低（P<0.001），肝脏胰岛素受体、NrF2和血红素加氧酶-1 mRNA表达显著增加（P<0.001），以及肝脏组织中NrF2的显著增加和核转位。
甘草酸改善了高脂饮食诱导的大鼠肥胖，这可能归因于其增加胰岛素受体表达以及激活NrF2和随后的血红素加氧酶-1途径的能力。因此，这项研究代表了一种安全的天然化合物（甘草酸），其在预防或治疗与肥胖相关的胰岛素抵抗方面具有重要作用。
