Treating obesity using the combination of metformin and epigallocatechin-3-gallate

Zhican YANG , Xinyuan ZHAO , Ying LIU , Benchi ZHAO , Yi LUO , Jiansheng KANG , Qiaoping WANG
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Abstract

Objective

This study aimed to investigate the anti-obesity effects of the combination of metformin and epigallocatechin-3-gallate (EGCG) in a diet-induced obese (DIO) model.

Methods

Male C57BL/6J mice were fed with high-fat diet (HFD, 60% fat) to establish a DIO model. The DIO mice were administered intragastrically daily with vehicle, metformin (Met, 250 mg/kg), EGCG (200 mg/kg), or mixture of Met and EGCG (Met/EGCG; 250 and 200 mg/kg) for 32 days. Body weight was measured daily at a fixed time point. An intraperitoneal glucose tolerance test was performed on day 26 after treatments. Body composition was determined by using nuclear magnetic resonance technology. Adipose tissues and major organs were collected after culling. Gene expression in brown adipose tissue (BAT) and subcutaneous white adipose tissue (scWAT) were detected by quantitative polymerase chain reaction.

Results

Compared with the vehicle group, the body weight was significantly reduced in DIO mice in the Met and Met/EGCG groups. The weight loss rate in the Met and EGCG groups were 9.1% and 1.0%, respectively. However, Met/EGCG induced a 14.0% body weight loss, suggesting that the combination of Met and EGCG has a synergistic effect on reversing the body weight in DIO mice. Met/EGCG demonstrated beneficial effects on the subcutaneous fat, BAT, and glucose homeostasis in DIO mice. Furthermore, Met/EGCG did not significantly increase the thermogenic gene expression in BAT, whereas in scWAT, Met/EGCG showed moderate effects on the expression of specific markers of browning fat or beige fat.

Conclusion

Metformin and EGCG have combined treatment effect on the body weight of DIO mice. Their combination might be a promising treatment approach for obesity.

二甲双胍联合没食子儿茶素-3-没食子酸酯治疗肥胖症
目的探讨二甲双胍联合没食子儿茶素-3-没食子酸酯(EGCG)对饮食性肥胖(DIO)模型的抗肥胖作用。方法采用高脂饲料(HFD, 60%脂肪)饲养C57BL/6J小鼠,建立DIO模型。DIO小鼠每天灌胃给药,分别给药剂、二甲双胍(Met, 250 mg/kg)、EGCG (200 mg/kg)或Met和EGCG的混合物(Met/EGCG;250和200 mg/kg),持续32天。每天在固定时间点测量体重。治疗后第26天进行腹腔葡萄糖耐量试验。采用核磁共振技术测定体成分。剔除后收集脂肪组织和主要器官。采用定量聚合酶链反应检测棕色脂肪组织(BAT)和皮下白色脂肪组织(scWAT)基因表达。结果与对照组相比,蛋氨酸组和蛋氨酸/EGCG组小鼠体重明显减轻。蛋氨酸组和EGCG组的减重率分别为9.1%和1.0%。然而,Met/EGCG诱导体重减轻14.0%,表明Met和EGCG联合使用对逆转DIO小鼠的体重具有协同作用。蛋氨酸/EGCG对DIO小鼠皮下脂肪、BAT和葡萄糖稳态有有益影响。此外,Met/EGCG并未显著增加BAT中产热基因的表达,而在scWAT中,Met/EGCG对褐变脂肪或米色脂肪特异性标志物的表达有中等影响。结论二甲双胍和EGCG对DIO小鼠体重有联合治疗作用。它们的结合可能是一种很有希望的治疗肥胖的方法。
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