Yang Wenqi, Chen Xu, Chen Ming, Li Yanping, Li Qing, Jiang Xinwei, Yang Yan, Ling Wenhua
Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, P. R. China.
Food Funct. 2017 Apr 19;8(4):1481-1493. doi: 10.1039/c6fo01841f.
The beneficial effects of fish oil consumption on glucose metabolism have been generally reported. However, the mechanism underlying the fish oil-induced protective effects against insulin resistance remains unclear. Endoplasmic reticulum (ER) stress is recognized as an important contributor to insulin resistance. The aim of this study is to evaluate whether fish oil supplementation reduces ER stress and ameliorates insulin resistance in diet-induced obese mice, and to investigate the molecular mechanism of fish oil-induced benefits on ER stress. C57BL/6J mice were fed one of the following diets for 12 weeks: the low-fat diet (LFD), the high-fat diet (HFD) or the fish oil-supplemented high-fat diet (FOD). Fish oil supplementation led to lower blood glucose, better glucose tolerance and improved insulin sensitivity in high-fat diet-induced obese mice. Importantly, fish oil administration inhibited high-fat feeding-induced ER stress and reduced adipose tissue dysfunction. The fish oil-induced improvements were accompanied by the elevation of phosphorylated AMP-activated protein kinase (AMPK) expression in white adipose tissue. Correspondingly, the results of in vitro experiments showed that docosahexaenoic acid (DHA), the main n-3 polyunsaturated fatty acid (PUFA) in the fish oil used in the study, led to a dose-dependent increase in AMPK phosphorylation and suppressed palmitic acid (PA)-triggered ER stress in differentiated 3T3-L1 adipocytes. Furthermore, AMPK inhibitor (compound C) treatment largely blocked the effects of DHA to inhibit PA-induced ER stress. Our data indicate that n-3 PUFAs suppress ER stress in adipocytes through AMPK activation, and may thereby exert protective effects against high-fat feeding-induced adipose tissue dysfunction and insulin resistance.
普遍报道了食用鱼油对葡萄糖代谢的有益作用。然而，鱼油诱导的抗胰岛素抵抗保护作用的潜在机制仍不清楚。内质网（ER）应激被认为是胰岛素抵抗的一个重要促成因素。本研究的目的是评估补充鱼油是否能减轻饮食诱导的肥胖小鼠的内质网应激并改善胰岛素抵抗，并探讨鱼油对内质网应激产生有益作用的分子机制。将C57BL/6J小鼠喂食以下饮食之一12周：低脂饮食（LFD）、高脂饮食（HFD）或补充鱼油的高脂饮食（FOD）。补充鱼油可降低高脂饮食诱导的肥胖小鼠的血糖，改善葡萄糖耐量并提高胰岛素敏感性。重要的是，给予鱼油可抑制高脂喂养诱导的内质网应激并减少脂肪组织功能障碍。鱼油诱导的改善伴随着白色脂肪组织中磷酸化AMP活化蛋白激酶（AMPK）表达的升高。相应地，体外实验结果表明，本研究中使用的鱼油中的主要n-3多不饱和脂肪酸（PUFA）二十二碳六烯酸（DHA）导致AMPK磷酸化呈剂量依赖性增加，并抑制分化的3T3-L1脂肪细胞中棕榈酸（PA）引发的内质网应激。此外，AMPK抑制剂（化合物C）处理在很大程度上阻断了DHA抑制PA诱导的内质网应激的作用。我们的数据表明，n-3多不饱和脂肪酸通过激活AMPK抑制脂肪细胞中的内质网应激，从而可能对高脂喂养诱导的脂肪组织功能障碍和胰岛素抵抗发挥保护作用。
