Liu Hui, Guan Hui, Tan Xintong, Jiang Yang, Li Feng, Sun-Waterhouse Dongxiao, Li Dapeng
College of Food Science and Engineering, Shandong Agricultural University, Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, Taian, 271018, PR China.
College of Food Science and Engineering, Shandong Agricultural University, Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, Taian, 271018, PR China.
Free Radic Biol Med. 2022 Mar;181:105-117. doi: 10.1016/j.freeradbiomed.2022.02.002. Epub 2022 Feb 4.
Quercetin and EGCG exhibit anti-diabetic and anti-obesity activities, however, their interactive effects in anti-diabetic/anti-obesity actions and underlying mechanisms remain unclear. This study aimed to fill these knowledge gaps. Quercetin, EGCG or their combination attenuated insulin resistance and decreased hepatic gluconeogenesis in high-fat-high-fructose diet (HFFD)-fed C57BL/6 mice and in palmitic acid (PA)-treated HepG2 cells. In mice, supplementation with quercetin (0.05%w/w), EGCG (0.05%w/w) and their combination (quercetin 0.05%+EGCG 0.05%w/w) reduced weight gain and fasting blood glucose and improved serum biochemical parameters. Compare with quercetin/EGCG alone, the quercetin-EGCG combination reduced gluconeogenesis to a greater extent via IRS-1/Akt/FOXO1-mediated down-regulation of downstream PEPCK and G-6-pase. In HepG2 cells, the quercetin (5 μM)-EGCG (5 μM) co-treatment exerted greater suppression on PA-induced changes in glucose and glycogen contents and hexokinase and G-6-pase activities than quercetin/EGCG alone (each 10 μM). The quercetin-EGCG co-treatment reduced glucose production through targeting FOXO1 and inhibiting the transcription of gluconeogenic enzymes. MiR-27a-3p and miR-96-5p regulated directly FOXO1 expression and function, and co-inhibition of miR-27a-3p and miR-96-5p weakened greatly the protective effect of quercetin-EGCG combination. This is the first report on the contributions of miR-27a-3p and miR-96-5p to the synergistic and protective effect of the quercetin-EGCG co-treatment against PA-induced insulin resistance through inhibiting FOXO1 expression.
槲皮素和表没食子儿没食子酸酯（EGCG）具有抗糖尿病和抗肥胖活性，然而，它们在抗糖尿病/抗肥胖作用及潜在机制中的相互作用仍不清楚。本研究旨在填补这些知识空白。槲皮素、EGCG或它们的组合可减轻高脂高果糖饮食（HFFD）喂养的C57BL/6小鼠以及棕榈酸（PA）处理的HepG2细胞中的胰岛素抵抗，并降低肝脏糖异生。在小鼠中，补充槲皮素（0.05%w/w）、EGCG（0.05%w/w）及其组合（槲皮素0.05%+EGCG 0.05%w/w）可减轻体重增加和空腹血糖，并改善血清生化参数。与单独使用槲皮素/EGCG相比，槲皮素-EGCG组合通过IRS-1/Akt/FOXO1介导的下游磷酸烯醇式丙酮酸羧激酶（PEPCK）和葡萄糖-6-磷酸酶（G-6-pase）下调，更大程度地降低糖异生。在HepG2细胞中，槲皮素（5 μM）-EGCG（5 μM）联合处理对PA诱导的葡萄糖和糖原含量变化以及己糖激酶和G-6-pase活性的抑制作用比单独使用槲皮素/EGCG（各10 μM）更强。槲皮素-EGCG联合处理通过靶向FOXO1并抑制糖异生酶的转录来减少葡萄糖生成。微小RNA-27a-3p（miR-27a-3p）和微小RNA-96-5p（miR-96-5p）直接调节FOXO1的表达和功能，同时抑制miR-27a-3p和miR-96-5p会大大削弱槲皮素-EGCG组合的保护作用。这是关于miR-27a-3p和miR-96-5p通过抑制FOXO1表达对槲皮素-EGCG联合处理对抗PA诱导的胰岛素抵抗的协同保护作用贡献的首篇报道。
