Isoquercitrin from Apocynum venetum L. produces an anti-obesity effect on obese mice by targeting C-1-tetrahydrofolate synthase, carbonyl reductase, and glutathione S-transferase P and modification of the AMPK/SREBP-1c/FAS/CD36 signaling pathway in mice in vivo
Isoquercitrin from Apocynum venetum L. produces an anti-obesity effect on obese mice by targeting C-1-tetrahydrofolate synthase, carbonyl reductase, and glutathione S-transferase P and modification of the AMPK/SREBP-1c/FAS/CD36 signaling pathway in mice in vivo
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罗布麻异槲皮苷通过靶向 C-1-四氢叶酸合酶、羰基还原酶和谷胱甘肽 S-转移酶 P 并修饰小鼠的 AMPK/SREBP-1c/FAS/CD36 信号通路，对肥胖小鼠产生抗肥胖作用
DOI：
10.1039/d2fo02438a
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发表时间：
2022-10-07
期刊：
影响因子：
6.1
通讯作者：
Qi, Jianhua
中科院分区：
文献类型：
--
作者：
Manzoor, Majid;Muroi, Makoto;Qi, Jianhua
在本研究中，使用高脂饮食诱导的肥胖小鼠来研究罗布麻水提取物和异槲皮苷的抗肥胖作用。水提取物和信号分子异槲皮苷显着降低肥胖小鼠的体重增加，食物摄入量，水消耗量，空腹血糖，血浆甘油三酯和总胆固醇水平。此外，通过RT-PCR分析和腺苷5 '-磷酸活化蛋白激酶（AMPK）和固醇调节元件结合蛋白（SREBP-1c）抑制剂及葡萄糖的摄取实验，探讨了异槲皮苷的作用机制。异槲皮苷可使肥胖小鼠SREBP-1c、脂肪酸合成酶（FAS）、硬脂酰辅酶A去饱和酶-1（SCD）和分化簇36（CD 36）等指标显著升高，但在给药后恢复至正常水平。AMPK和SREBP-1c抑制剂可降低异槲皮苷的减肥作用。此外，口服异槲皮苷后，正常小鼠的肠道葡萄糖摄取明显受到抑制。此外，基于二维凝胶电泳的全蛋白质组细胞热位移分析（CETSA）表明，异槲皮苷的潜在靶蛋白是C-1-四氢叶酸合成酶，羰基还原酶，这些结果表明，异槲皮苷通过靶向上述蛋白质并调节AMPK/SREBP-1c信号通路而产生抗肥胖作用，并潜在地预防肥胖和肥胖症。相关的代谢紊乱。
In the present study, mice with high-fat-diet-induced obesity were used in investigating the anti-obesity effects of an aqueous extract and isoquercitrin from Apocynum venetum L. The aqueous extract and the signal molecule isoquercitrin significantly reduced the body weight gain, food intake, water consumption, and fasting blood glucose, plasma triglyceride and total cholesterol levels of the obese mice. Furthermore, the mechanism of action of isoquercitrin was explored through RT-PCR analyses and uptake experiments of adenosine 5'-monophosphate-activated protein kinase (AMPK) and sterol regulatory-element binding protein (SREBP-1c) inhibitors and glucose. The indexes of SREBP-1c, fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD), and cluster of differentiation 36 (CD36) in obese mice significantly increased but returned to normal levels after the administration of isoquercitrin. Meanwhile, the anti-obesity effect of isoquercitrin was diminished by the inhibitors of AMPK and SREBP-1c. In addition, intestinal glucose uptake in normal mice was significantly inhibited after the oral administration of isoquercitrin. Moreover, 2D gel electrophoresis based proteome-wide cellular thermal shift assay (CETSA) showed that the potential target proteins of isoquercitrin were C-1-tetrahydrofolate synthase, carbonyl reductase, and glutathione S-transferase P. These results suggested that isoquercitrin produces an anti-obesity effect by targeting the above-mentioned proteins and regulating the AMPK/SREBP-1c signaling pathway and potentially prevents obesity and obesity-related metabolic disorders.