Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa.
Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa.
Molecules. 2020 Apr 13;25(8):1773. doi: 10.3390/molecules25081773.
The current study explored the effect of isoorientin on the metabolic activity and lipid accumulation in fully differentiated 3T3-L1 adipocytes. To achieve this, the 3T3-L1 pre-adipocytes were differentiated for eight days and treated with various concentrations of isoorientin (0.1-100 μM) for four hours. Subsequently, the metabolic activity, lipid accumulation, and mitochondrial respiration were assessed. Furthermore, to unravel the molecular mechanisms that might elucidate the bioactivity of isoorientin, protein expression of the genes involved in insulin signaling and energy expenditure, such as AKT and AMPK, were investigated. The results showed that isoorientin, at different doses, could block lipid storage and enhance glycerol release, with a concomitant improvement of the metabolic activity and mitochondrial function. Although the observed beneficial effects of isoorientin on these cultured 3T3-L1 adipocytes were not consistent at all concentrations, it was clear that doses between 1 and 10 μM were most effective compared to the untreated control. Moreover, the activity of isoorientin was comparable to tested positive controls of CL-316,2431, isoproterenol, insulin, and metformin. Mechanistically, protein expression of AKT and AMPK, was enhanced with isoorientin exposure, suggesting their partial role in modulating lipid metabolism and mitochondrial biogenesis. Indeed, our results showed that isoorientin has the ability to enhance mitochondrial respiration, as we observed an increase in the ATP and oxygen consumption rate. Therefore, we concluded that isoorientin has a potential to impact mitochondrial activity, lipid metabolism and energy expenditure using an in vitro experimental model of obesity.
本研究旨在探讨鸢尾黄素对完全分化的 3T3-L1 脂肪细胞代谢活性和脂质积累的影响。为此，将 3T3-L1 前脂肪细胞分化 8 天，并用不同浓度的鸢尾黄素（0.1-100 μM）处理 4 小时。随后，评估了代谢活性、脂质积累和线粒体呼吸。此外，为了阐明可能阐明鸢尾黄素生物活性的分子机制，研究了参与胰岛素信号和能量消耗的基因（如 AKT 和 AMPK）的蛋白表达。结果表明，鸢尾黄素在不同剂量下可以阻断脂质储存并促进甘油释放，同时改善代谢活性和线粒体功能。尽管在所有浓度下都未观察到鸢尾黄素对这些培养的 3T3-L1 脂肪细胞的有益作用，但很明显，与未处理的对照组相比，1 至 10 μM 之间的剂量最为有效。此外，鸢尾黄素的活性与测试的阳性对照物 CL-3162431、异丙肾上腺素、胰岛素和二甲双胍相当。从机制上讲，AKT 和 AMPK 的蛋白表达随着鸢尾黄素的暴露而增强，表明它们在调节脂质代谢和线粒体生物发生方面发挥了部分作用。事实上，我们的结果表明，鸢尾黄素能够增强线粒体呼吸，因为我们观察到 ATP 和耗氧量增加。因此，我们得出结论，鸢尾黄素具有通过肥胖的体外实验模型影响线粒体活性、脂质代谢和能量消耗的潜力。
