Flachs P, Mohamed-Ali V, Horakova O, Rossmeisl M, Hosseinzadeh-Attar M J, Hensler M, Ruzickova J, Kopecky J
Department of Adipose Tissue Biology, Institute of Physiology, Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.
Diabetologia. 2006 Feb;49(2):394-7. doi: 10.1007/s00125-005-0053-y. Epub 2006 Jan 6.
AIMS/HYPOTHESIS: Diets rich in n-3 polyunsaturated fatty acids, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against insulin resistance and obesity in rodents and increase insulin sensitivity in healthy humans. We tested whether the anti-diabetic effects of EPA and DHA involve enhanced production of the endogenous insulin sensitiser, adiponectin.
We studied the effects, in an obesity-promoting high-fat diet, of partial replacement of vegetable oils by EPA/DHA concentrate (6% EPA, 51% DHA) over a 5-week period in adult male C57BL/6J mice that either had free access to food or had their food intake restricted by 30%. At the end of the treatment, systemic markers of lipid and glucose metabolism and full-length adiponectin and leptin were measured. Adiponectin (Adipoq) and leptin (Lep) gene expression in dorsolumbar and epididymal white adipose tissue (WAT) and isolated adipocytes was quantified and adipokine production from WAT explants evaluated.
In mice with free access to food, plasma triacylglycerols, NEFA, and insulin levels were lower in the presence of EPA/DHA, while glucose and leptin levels were not significantly altered. Food restriction decreased plasma triacylglycerols, glucose, insulin and leptin, but not adiponectin. EPA/DHA increased plasma adiponectin levels, independent of food intake, reflecting the stimulation of Adipoq expression in adipocytes and the release of adiponectin from WAT, particularly from epididymal fat. Expression of Lep and the release of leptin from WAT, while being extremely sensitive to caloric restriction, was unaltered by EPA/DHA.
CONCLUSIONS/INTERPRETATION: Intake of diets rich in EPA and DHA leads to elevated systemic concentrations of adiponectin, largely independent of food intake or adiposity and explain, to some extent, their anti-diabetic effects.
目的/假设：富含n-3多不饱和脂肪酸（即二十碳五烯酸（EPA）和二十二碳六烯酸（DHA））的饮食可预防啮齿动物的胰岛素抵抗和肥胖，并提高健康人的胰岛素敏感性。我们测试了EPA和DHA的抗糖尿病作用是否涉及内源性胰岛素增敏剂脂联素的产生增加。
我们研究了在促肥胖的高脂饮食中，用EPA/DHA浓缩物（6% EPA，51% DHA）部分替代植物油，对成年雄性C57BL/6J小鼠为期5周的影响，这些小鼠要么可自由进食，要么食物摄入量受限30%。在治疗结束时，测量脂质和葡萄糖代谢的全身标志物以及全长脂联素和瘦素。对背腰部和附睾白色脂肪组织（WAT）以及分离的脂肪细胞中的脂联素（Adipoq）和瘦素（Lep）基因表达进行定量，并评估WAT外植体的脂肪因子产生。
在可自由进食的小鼠中，存在EPA/DHA时血浆三酰甘油、非酯化脂肪酸（NEFA）和胰岛素水平较低，而葡萄糖和瘦素水平无显著变化。食物限制降低了血浆三酰甘油、葡萄糖、胰岛素和瘦素，但未降低脂联素。EPA/DHA增加了血浆脂联素水平，与食物摄入量无关，这反映了对脂肪细胞中Adipoq表达的刺激以及脂联素从WAT（特别是附睾脂肪）的释放。Lep的表达以及瘦素从WAT的释放虽然对热量限制极为敏感，但不受EPA/DHA的影响。
结论/解读：摄入富含EPA和DHA的饮食会导致全身脂联素浓度升高，很大程度上与食物摄入量或肥胖无关，这在一定程度上解释了它们的抗糖尿病作用。
