Muurling Martin, Mensink Ronald P, Pijl Hanno, Romijn Johannes A, Havekes Louis M, Voshol Peter J
TNO-Prevention and Health, Gaubius Laboratory Leiden, 2301 CE Leiden, The Netherlands.
J Nutr. 2003 Nov;133(11):3350-5. doi: 10.1093/jn/133.11.3350.
Dietary interventions with fish oil have been found to protect against the development of high-fat diet-induced insulin resistance and to decrease the expression of tumor necrosis factor (TNF)-alpha. However, the effect of fish oil administration on preexisting insulin resistance is subject to debate. In the present study, we examined the mechanism by which fish oil affects preexisting insulin resistance. High fat diet-induced insulin-resistant ApoE*3-Leiden transgenic mice were treated for 10 wk as follows: 1) high fat diet (control group), 2) high fat diet with 3 g/100 g fish oil and 3) high fat diet but food intake restricted to 75% of the ad libitum food intake. We measured plasma glucose, insulin, free fatty acids (FFA) and triglyceride (TG) levels throughout the study. After the 10-wk dietary intervention period we performed hyperinsulinemic euglycemic analyses and measured insulin sensitivity and FFA turnover. Furthermore, we then determined the VLDL-TG production rate and TNF-alpha protein expression in white adipose tissue (WAT). Compared with control mice, the insulin sensitivity of mice treated with fish oil was not affected, whereas it was improved (P < 0.05) for energy-restricted mice. FFA turnover was unaffected in both fish oil-treated and energy-restricted mice. Compared with controls, hepatic VLDL-TG production was lower (P < 0.05) with fish oil feeding but greater with energy restriction (P < 0.05). Interestingly, the level of TNF-alpha protein in WAT was lower (P < 0.05) in both groups. We conclude that partial replacement of saturated fat by fish oil does not improve preexisting high fat diet-induced insulin resistance, although it lowers TNF-alpha protein levels in WAT.
已发现用鱼油进行饮食干预可预防高脂饮食诱导的胰岛素抵抗的发展，并降低肿瘤坏死因子（TNF）-α的表达。然而，给予鱼油对已存在的胰岛素抵抗的影响仍存在争议。在本研究中，我们研究了鱼油影响已存在的胰岛素抵抗的机制。将高脂饮食诱导的胰岛素抵抗ApoE*3-莱顿转基因小鼠按以下方式处理10周：1）高脂饮食（对照组），2）含3 g/100 g鱼油的高脂饮食，3）高脂饮食但食物摄入量限制为自由摄食摄入量的75%。在整个研究过程中，我们测量了血浆葡萄糖、胰岛素、游离脂肪酸（FFA）和甘油三酯（TG）水平。在10周的饮食干预期后，我们进行了高胰岛素正常血糖分析，并测量了胰岛素敏感性和FFA周转率。此外，我们随后测定了白色脂肪组织（WAT）中极低密度脂蛋白-甘油三酯（VLDL-TG）的产生率和TNF-α蛋白表达。与对照小鼠相比，用鱼油处理的小鼠的胰岛素敏感性未受影响，而能量限制小鼠的胰岛素敏感性得到改善（P<0.05）。在鱼油处理组和能量限制组小鼠中，FFA周转率均未受影响。与对照组相比，喂食鱼油时肝脏VLDL-TG的产生较低（P<0.05），而能量限制时则较高（P<0.05）。有趣的是，两组WAT中TNF-α蛋白水平均较低（P<0.05）。我们得出结论，尽管鱼油可降低WAT中TNF-α蛋白水平，但用鱼油部分替代饱和脂肪并不能改善已存在的高脂饮食诱导的胰岛素抵抗。
