Ibrahim Ahamed, Natarajan Saravanan
Department of Biochemistry, National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania P.O., Hyderabad-500 007, A.P., India.
Biochim Biophys Acta. 2005 Mar 21;1733(1):67-75. doi: 10.1016/j.bbalip.2004.12.003.
This study describes the effect of substituting dietary linoleic acid (18:2 n-6) with alpha-linolenic acid (18:3 n-3) on sucrose-induced insulin resistance (IR). Wistar NIN male weanling rats were fed casein based diet containing 22 energy percent (en%) fat with approximately 6, 9 and 7 en% saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) respectively for 3 months. IR was induced by replacing starch (ST) with sucrose (SU). Blends of groundnut, palmolein, and linseed oil in different proportions furnished the following levels of 18:3 n-3 (g/100 g diet) and 18:2 n-6/18:3 n-3 ratios respectively: ST-220 (0.014, 220), SU-220 (0.014, 220), SU-50 (0.06, 50), SU-10 (0.27, 10) and SU-2 (1.1, 2). The results showed IR in the sucrose fed group (SU-220) as evidenced by increase in fasting plasma insulin and area under the curve (AUC) of insulin in response to oral glucose load. In SU-220, the increase in adipocyte plasma membrane cholesterol/phospholipid ratio was associated with a decrease in fluidity, insulin stimulated glucose transport, antilipolytic effect of insulin and increase in basal and norepinephrine stimulated lipolysis in adipocytes. In SU-50, sucrose induced alterations in adipocyte lipolysis and antilipolysis were normalized. However, in SU-2, partial corrections in plasma insulin, AUC of insulin and adipocyte insulin stimulated glucose transport were observed. Further, plasma triglycerides and cholesterol decreased in SU-2. In diaphragm phospholipids, the observed dose dependent increase in long chain (LC) n-3 PUFA was associated with a decrease in LC-n-6 PUFA but insulin stimulated glucose transport increased only in SU-2. Thus, this study shows that the substitution of one-third of dietary 18:2 n-6 with 18:3 n-3 (SU-2) results in lowered blood lipid levels and increases peripheral insulin sensitivity, possibly due to the resulting high LCn-3 PUFA levels in target tissues of insulin action. These findings suggest a role for 18:3 n-3 in the prevention of insulin resistant states. The current recommendation to increase 18:3 n-3 intake for reducing cardiovascular risk may also be beneficial for preventing IR in humans.
本研究描述了用α-亚麻酸（18:3 n-3）替代膳食亚油酸（18:2 n-6）对蔗糖诱导的胰岛素抵抗（IR）的影响。将Wistar NIN雄性断奶大鼠喂食以酪蛋白为基础的饮食，该饮食含有22能量百分比（en%）的脂肪，其中饱和脂肪酸（SFA）、单不饱和脂肪酸（MUFA）和多不饱和脂肪酸（PUFA）分别约为6 en%、9 en%和7 en%，持续3个月。通过用蔗糖（SU）替代淀粉（ST）诱导IR。不同比例的花生油、棕榈油和亚麻籽油混合物分别提供了以下水平的18:3 n-3（克/100克饮食）和18:2 n-6/18:3 n-3比率：ST-220（0.014，220）、SU-220（0.014，220）、SU-50（0.06，50）、SU-10（0.27，10）和SU-2（1.1，2）。结果显示，喂食蔗糖的组（SU-220）出现了IR，这通过空腹血浆胰岛素的增加以及口服葡萄糖负荷后胰岛素曲线下面积（AUC）得以证明。在SU-220中，脂肪细胞质膜胆固醇/磷脂比率的增加与流动性降低、胰岛素刺激的葡萄糖转运、胰岛素的抗脂解作用以及脂肪细胞基础和去甲肾上腺素刺激的脂解增加有关。在SU-50中，蔗糖诱导的脂肪细胞脂解和抗脂解改变恢复正常。然而，在SU-2中，观察到血浆胰岛素、胰岛素AUC和脂肪细胞胰岛素刺激的葡萄糖转运有部分改善。此外，SU-2中的血浆甘油三酯和胆固醇降低。在膈肌磷脂中，观察到长链（LC）n-3多不饱和脂肪酸的剂量依赖性增加与LC-n-6多不饱和脂肪酸的减少有关，但胰岛素刺激的葡萄糖转运仅在SU-2中增加。因此，本研究表明，用18:3 n-3替代三分之一的膳食18:2 n-6（SU-2）可降低血脂水平并增加外周胰岛素敏感性，这可能是由于胰岛素作用靶组织中产生的高LCn-3多不饱和脂肪酸水平所致。这些发现表明18:3 n-3在预防胰岛素抵抗状态中发挥作用。目前关于增加18:3 n-3摄入量以降低心血管风险的建议可能也有利于预防人类IR。
