小麦烷基间苯二酚对3T3-L1脂肪细胞胰岛素抵抗改善作用及机制

Protective Effect and Mechanism of Wheat Alkylresorcinols on Insulin Resistance in 3T3-L1 Adipocytes

低度慢性炎症状态是肥胖导致机体胰岛素抵抗的重要原因之一。小麦烷基间苯二酚(alkylresorcinols,ARs)是全麦食品膳食的生物标记物和重要的活性功能成分。利用体外炎症因子诱导,建立3T3-L1成熟脂肪细胞胰岛素抵抗模型,通过检测脂肪细胞脂质分解和葡萄糖吸收与利用情况,探讨小麦ARs在炎症状态下对脂肪细胞胰岛素抵抗的保护机制。研究结果表明:不同浓度小麦ARs(5~20μmol/L)干预能够剂量依赖性地改善炎症因子诱导的3T3-L1脂肪细胞胰岛素抵抗,脂肪细胞对葡萄糖利用率分别提升了4.3%、10.2%和24.0%;小麦ARs可以显著缓解炎症因子导致的脂肪细胞脂质分解。进一步机制解析发现:炎症因子显著降低了脂肪细胞糖代谢两个关键蛋白Akt的磷酸化(p-Akt)及其下游GLUT4蛋白表达,导致其葡萄糖利用障碍,而ARs干预显著提升了这两个蛋白的表达;采用PI3K抑制剂(LY294002)预处理脂肪细胞后,ARs对于脂肪细胞p-Akt及GLUT4表达的增加被抑制,相应的对于葡萄糖吸收的改善作用也被显著降低,脂肪细胞脂质分解增加,表明ARs通过特异性激活p-Akt/GLUT4信号通路改善了3T3-L1脂肪细胞胰岛素抵抗。最后,研究了小麦ARs的5种主要单体成分分别对于脂肪细胞胰岛素抵抗的改善作用,结果表明,十七烷基间苯二酚是小麦ARs发挥生理功能的主要活性物质。

Obesity is associated with a state of low-grade chronic inflammation that leads to impairment of insulin signaling pathway.Wheat alkylresorcinols(ARs)are biomarkers and active ingrendients of whole wheat food.In this study,inflammatory factors were used to establish the insulin resistant model in 3T3-L1 adipocytes in vitro,and the protective effect of wheat ARs on insulin resistance of adipocytes in inflammatory state was investigated by measuring the level of lipolysis and glucose uptake of adipocytes.The results showed that wheat ARs had no toxic effect on adipocytes at the concentration of 5~20μmol/L and could improve insulin resistance in 3T3-L1 adipocytes induced by inflammatory factors in a dose-dependent manner,and the glucose uptake increased by 4.3%,10.2%and 24.0%,respectively.Meanwhile,wheat ARs could significantly alleviate the lipolysis of adipocytes induced by inflammatory factors.In addition,the phosphorylation of Akt(p-Akt)and the expression of its downstream GLUT4 protein in adipocyte glycometa-bolism were significantly reduced by inflammatory factors,leading to glucose uptake disorder.ARs treatment significantly increased Akt phosphorylation and GLUT4 protein expression.After pre-treated with PI3K inhibitor(LY294002),the protective effect of ARs was reversed on 3T3-L1 adipocytes.The phosphorylation of Akt and the expression of its downstream protein GLUT4 were significantly inhibited.Additionally,the lipid accumulation and glucose uptake of adipocytes was inhibited by LY294002,which indicated that ARs could improve insulin resistance and lipolysis of adipocytes via activating p-Akt/GLUT4 signaling pathway.Furthermore,the protective effects of five major homologues of wheat ARs on insulin resistance of adipocytes were compared.These results indicated that heptadecylresorcinol(AR-C17)was the main active substance of wheat ARs.