Lamantia Valérie, Bissonnette Simon, Wassef Hanny, Cyr Yannick, Baass Alexis, Dufour Robert, Rabasa-Lhoret Rémi, Faraj May
Nutrition Department, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada; Montreal Diabetes Research Center (MDRC), Montréal, Québec, Canada.
Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada; Montreal Diabetes Research Center (MDRC), Montréal, Québec, Canada.
J Clin Lipidol. 2017 Jan-Feb;11(1):34-45.e2. doi: 10.1016/j.jacl.2016.09.013. Epub 2016 Oct 3.
Elevated plasma apoB is an independent predictor of T2D; however, underlying mechanisms remain unclear. Chronic reduction in white adipose tissue (WAT) function promotes T2D. We reported that differentiation of preadipocytes and acute incubation of human WAT with LDL induce their dysfunction (decreased hydrolysis and storage of triglyceride-rich lipoproteins [TRL]).
To examine the hypothesis that the association of plasma apoB with T2D risk factors, hypertriglyceridemia (hyperTG), insulin resistance (IR), and hyperinsulinemia, was dependent on WAT dysfunction.
Thirty normoglycemic subjects were enrolled (≥27 kg/m, 45-74 years). Fasting gynoid WAT biopsy was obtained followed by the ingestion of a C-triolein-labeled-high-fat meal. WAT function was measured ex vivo as the hydrolysis and storage of H-triolein-labeled-TRL as H-lipids over 4 hours. Insulin sensitivity and secretion were measured by Botnia clamps.
WAT function correlated with higher insulin sensitivity (M/I r = 0.60) and faster plasma clearance of chylomicrons in women (iAUC apoB48, r = -0.60). Plasma apoB correlated with WAT dysfunction (r = -0.52), postprandial hyperTG (iAUC-TG, r = 0.51, C-TG, r = 0.48), IR (M/I r = -0.38) and hyperinsulinemia (second phase-glucose-induced-insulin-secretion, r = 0.41). Co-incubation of subjects' WAT with their LDL increased medium accumulation of H-TRL and H-NEFA with no sex differences. Adjusting for WAT function eliminated the association of plasma apoB with IR independent of sex and body fat or adipocyte diameter. Its association with other risk factors was unaffected.
Association of plasma apoB with IR in obese subjects is dependent on gynoid WAT dysfunction. We propose that targeting hyperapoB, without increasing their uptake into nonhepatic peripheral tissues, ameliorates WAT function and risk for T2D.
血浆载脂蛋白B（apoB）升高是2型糖尿病（T2D）的独立预测指标；然而，其潜在机制仍不清楚。白色脂肪组织（WAT）功能的慢性降低会促进T2D的发生。我们报道过，前脂肪细胞的分化以及人WAT与低密度脂蛋白（LDL）的急性孵育会导致其功能障碍（富含甘油三酯的脂蛋白[TRL]的水解和储存减少）。
检验血浆apoB与T2D风险因素（高甘油三酯血症[高TG]、胰岛素抵抗[IR]和高胰岛素血症）之间的关联是否依赖于WAT功能障碍这一假设。
招募了30名血糖正常的受试者（体重指数≥27kg/m²，年龄45 - 74岁）。在摄入C - 三油酸甘油酯标记的高脂餐之前，获取空腹的腹部WAT活检样本。通过体外测量H - 三油酸甘油酯标记的TRL作为H - 脂质在4小时内的水解和储存来评估WAT功能。通过Botnia钳夹法测量胰岛素敏感性和分泌。
WAT功能与较高的胰岛素敏感性（M/I r = 0.60）以及女性乳糜微粒更快的血浆清除率相关（iAUC apoB48，r = -0.60）。血浆apoB与WAT功能障碍（r = -0.52）、餐后高TG（iAUC - TG，r = 0.51，C - TG，r = 0.48）、IR（M/I r = -0.38）和高胰岛素血症（第二阶段葡萄糖诱导的胰岛素分泌，r = 0.41）相关。受试者的WAT与其LDL共同孵育会增加H - TRL和H - NEFA在培养基中的积累，且无性别差异。校正WAT功能后，消除了血浆apoB与IR之间的关联，且不受性别、体脂或脂肪细胞直径的影响。其与其他风险因素的关联未受影响。
肥胖受试者中血浆apoB与IR之间的关联依赖于腹部WAT功能障碍。我们提出，在不增加其被非肝脏外周组织摄取的情况下，针对高apoB进行干预可改善WAT功能并降低T2D风险。
