Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India.
Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
Naunyn Schmiedebergs Arch Pharmacol. 2020 Nov;393(11):2093-2106. doi: 10.1007/s00210-020-01919-w. Epub 2020 Jun 25.
In metabolic disorders like obesity, NAFLD and T2DM, adipocytes are dysfunctional. Hence, pharmacological interventions have importance in preventing differentiation of adipocytes and stimulating lipid uptake. We, therefore, investigated the effects of arbutin (ARB), purpurin (PUR), quercetin (QR), and pterostilbene (PTS) on adipocyte differentiation and lipid uptake using 3T3-L1 adipocytes. Further, in silico docking studies were achieved to investigate interactions of ARB, PUR, QR, and PTS with beta-ketoacyl reductase (KR) and thioesterase (TE) domains of fatty acid synthase (FAS) enzyme. Mature 3T3-L1 adipocytes were used to investigate the anti-adipogenic effect of selected pharmacological agents by Oil Red O staining and in vitro fatty acid uptake analysis. Molecular docking studies were performed to predict the binding interactions of selected compounds with KR and TE domains of FAS enzyme. All these agents significantly decrease the adipocyte differentiation and showed the stimulatory effect on fatty acid uptake in 3T3-L1 adipocytes. However, PTS and PUR proved to be anti-adipogenic, whereas ARB and QR showed significant effect on fatty acid uptake, compared to others. Similarly, all the compounds displayed significant binding interactions with KR and TE domains of FAS enzyme, supporting the results of in vitro studies. Graphical abstract.
在代谢紊乱疾病如肥胖症、非酒精性脂肪性肝病和 2 型糖尿病中，脂肪细胞功能失调。因此，药理学干预在预防脂肪细胞分化和刺激脂质摄取方面具有重要意义。因此，我们使用 3T3-L1 脂肪细胞研究了熊果苷（ARB）、紫珠素（PUR）、槲皮素（QR）和紫檀芪（PTS）对脂肪细胞分化和脂质摄取的影响。此外，还进行了计算机对接研究，以研究 ARB、PUR、QR 和 PTS 与脂肪酸合成酶（FAS）酶的β-酮酰基还原酶（KR）和硫酯酶（TE）结构域的相互作用。使用成熟的 3T3-L1 脂肪细胞通过油红 O 染色和体外脂肪酸摄取分析研究选定药理试剂的抗脂肪生成作用。进行分子对接研究以预测所选化合物与 FAS 酶的 KR 和 TE 结构域的结合相互作用。所有这些试剂均显著降低脂肪细胞分化，并在 3T3-L1 脂肪细胞中显示出对脂肪酸摄取的刺激作用。然而，与其他试剂相比，PTS 和 PUR 被证明具有抗脂肪生成作用，而 ARB 和 QR 则对脂肪酸摄取有显著影响。同样，所有化合物均与 FAS 酶的 KR 和 TE 结构域显示出显著的结合相互作用，支持了体外研究的结果。
