Faculty of Medicine, Université de Montréal, Montréal, Québec.
Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Québec.
J Nutr. 2019 Jan 1;149(1):57-67. doi: 10.1093/jn/nxy238.
δ-5 and δ-6 desaturases (D5D and D6D) catalyze the endogenous conversion of n-3 (ω-3) and n-6 (ω-6) polyunsaturated fatty acids (PUFAs). Their activities are negatively and positively associated with type 2 diabetes (T2D), respectively, by unclear mechanisms. Elevated plasma apoB-lipoproteins (measured as plasma apoB), which can be reduced by n-3 PUFA intake, promote T2D risk factors.
The aim of this study was to test the hypothesis that the association of D5D and D6D activities with T2D risk factors is dependent on plasma apoB.
This is a pooled analysis of 2 populations recruited for 2 different metabolic studies. It is a post hoc analysis of baseline data of these subjects [n = 98; 60% women (postmenopausal); mean ± SD body mass index (in kg/m2): 32.8 ± 4.7; mean ± SD age: 57.6 ± 6.3 y]. Glucose-induced insulin secretion (GIIS) and insulin sensitivity (IS) were measured using Botnia clamps. Plasma clearance of a high-fat meal (600 kcal/m2, 66% fat) and white adipose tissue (WAT) function (storage of 3H-triolein-labeled substrate) were assessed in a subpopulation (n = 47). Desaturase activities were estimated from plasma phospholipid fatty acids. Associations were examined using Pearson and partial correlations.
While both desaturase activities were positively associated with percentage of eicosapentaenoic acid, only D5D was negatively associated with plasma apoB (r = -0.30, P = 0.003). Association of D5D activity with second-phase GIIS (r = -0.23, P = 0.029), IS (r = 0.33, P = 0.015, in women) and 6-h area-under-the-curve (AUC6h) of plasma chylomicrons (apoB48, r = -0.47, P = 0.020, in women) was independent of age and adiposity, but was eliminated after adjustment for plasma apoB. D6D activity was associated in the opposite direction with GIIS (r = 0.24, P = 0.049), IS (r = -0.36, P = 0.004) and AUC6h chylomicrons (r = 0.52, P = 0.004), independent of plasma apoB. Both desaturases were associated with plasma interleukin-1-receptor antagonist (D5D: r = -0.45, P < 0.001 in women; D6D: r = -0.33, P = 0.007) and WAT function (trend for D5D: r = 0.30, P = 0.05; D6D: r = 0.39, P = 0.027) independent of any adjustment.
Association of D5D activity with IS, lower GIIS, and plasma chylomicron clearance is dependent on plasma apoB in overweight and obese adults.
δ-5 和 δ-6 去饱和酶（D5D 和 D6D）催化 n-3（ω-3）和 n-6（ω-6）多不饱和脂肪酸（PUFA）的内源性转化。它们的活性分别通过不清楚的机制与 2 型糖尿病（T2D）呈负相关和正相关。升高的载脂蛋白 B-脂蛋白（以血浆载脂蛋白 B 测量），可以通过 n-3 PUFA 摄入减少，促进 T2D 风险因素。
本研究旨在检验 D5D 和 D6D 活性与 T2D 风险因素的关联取决于血浆载脂蛋白 B 的假设。
这是针对两个不同代谢研究招募的两个人群的汇总分析。这是对这些受试者基线数据的事后分析[n=98；60%女性（绝经后）；平均±SD 体重指数（kg/m2）：32.8±4.7；平均±SD 年龄：57.6±6.3 y]。使用 Botnia 夹钳测量葡萄糖诱导的胰岛素分泌（GIIS）和胰岛素敏感性（IS）。在亚组（n=47）中评估了高脂肪餐（600 千卡/m2，66%脂肪）和白色脂肪组织（WAT）功能（3H-三油酸标记底物的储存）的清除率。通过血浆磷脂脂肪酸估计去饱和酶活性。使用 Pearson 和偏相关进行关联检验。
虽然两种去饱和酶活性均与二十碳五烯酸的百分比呈正相关，但只有 D5D 与血浆载脂蛋白 B 呈负相关（r=-0.30，P=0.003）。D5D 活性与第二相 GIIS（r=-0.23，P=0.029）、IS（r=0.33，P=0.015，女性）和 6 小时 AUC6h 血浆乳糜微粒（载脂蛋白 B48，r=-0.47，P=0.020，女性）的关联独立于年龄和肥胖，但在调整血浆载脂蛋白 B 后消除。D6D 活性呈相反方向与 GIIS（r=0.24，P=0.049）、IS（r=-0.36，P=0.004）和 AUC6h 乳糜微粒（r=0.52，P=0.004）相关，独立于血浆载脂蛋白 B。两种去饱和酶均与血浆白细胞介素-1 受体拮抗剂（D5D：女性 r=-0.45，P<0.001；D6D：r=-0.33，P=0.007）和 WAT 功能（D5D 趋势：r=0.30，P=0.05；D6D：r=0.39，P=0.027）相关，独立于任何调整。
在超重和肥胖成年人中，D5D 活性与 IS、较低的 GIIS 和血浆乳糜微粒清除率的关联取决于血浆载脂蛋白 B。
