Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Obesity (Silver Spring). 2011 Nov;19(11):2235-40. doi: 10.1038/oby.2011.107. Epub 2011 May 5.
Bariatric surgery is associated with near immediate remission of type 2 diabetes and hyperlipidemia. The mechanisms underlying restoration of normal glucose tolerance postoperatively are poorly understood. Herein, we examined the effect of Roux-en-Y gastric bypass surgery (RYGB) on weight loss, insulin sensitivity, plasma ceramides, proinflammatory markers, and cardiovascular risk factors before and at 3 and 6 months after surgery. Thirteen patients (10 female; age 48.5 ± 2.7 years; BMI, 47.4 ± 1.5 kg/m(2)) were included in the study, all of whom had undergone laparoscopic RYGB surgery. Insulin sensitivity, inflammatory mediators and fasting lipid profiles were measured at baseline, 3 and 6 months postoperatively, using enzymatic analysis. Plasma ceramide subspecies (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1) were quantified using electrospray ionization tandem mass spectrometry after separation with HPLC. At 3 months postsurgery, body weight was reduced by 25%, fasting total cholesterol, triglycerides, low-density lipoproteins, and free fatty acids were decreased, and insulin sensitivity was increased compared to presurgery values. These changes were all sustained at 6 months. In addition, total plasma ceramide levels decreased significantly postoperatively (9.3 ± 0.5 nmol/ml at baseline vs. 7.6 ± 0.4 at 3 months, and 7.3 ± 0.3 at 6 months, P < 0.05). At 6 months, the improvement in insulin sensitivity correlated with the change in total ceramide levels (r = -0.68, P = 0.02), and with plasma tumor necrosis factor-α (TNF-α) (r = -0.62, P = 0.04). We conclude that there is a potential role for ceramide lipids as mediators of the proinflammatory state and improved insulin sensitivity after gastric bypass surgery.
减重手术与 2 型糖尿病和血脂异常的即刻缓解相关。术后糖耐量恢复正常的机制尚不清楚。在此，我们研究了 Roux-en-Y 胃旁路手术（RYGB）对 13 名患者（10 名女性；年龄 48.5±2.7 岁；BMI，47.4±1.5kg/m2）的体重减轻、胰岛素敏感性、血浆神经酰胺、促炎标志物和心血管危险因素的影响，这些患者均接受了腹腔镜 RYGB 手术。使用酶分析法在基线、术后 3 个月和 6 个月时测量胰岛素敏感性、炎症介质和空腹血脂谱。使用高效液相色谱法分离后，用电喷雾串联质谱法定量测定血浆神经酰胺亚种（C14:0、C16:0、C18:0、C18:1、C20:0、C24:0 和 C24:1）。术后 3 个月，体重减轻 25%，空腹总胆固醇、甘油三酯、低密度脂蛋白和游离脂肪酸降低，胰岛素敏感性较术前增加。这些变化在 6 个月时仍持续存在。此外，术后总血浆神经酰胺水平显著降低（基线时为 9.3±0.5nmol/ml，术后 3 个月时为 7.6±0.4nmol/ml，术后 6 个月时为 7.3±0.3nmol/ml，P<0.05）。6 个月时，胰岛素敏感性的改善与总神经酰胺水平的变化（r=-0.68，P=0.02）以及血浆肿瘤坏死因子-α（TNF-α）（r=-0.62，P=0.04）呈负相关。我们的结论是，神经酰胺脂质可能作为胃旁路手术后促炎状态和改善胰岛素敏感性的介质发挥作用。
