Gastric Bypass Surgery Reduces Plasma Ceramide Subspecies and Improves Insulin Sensitivity in Severely Obese Patients

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-alpha (TNF-alpha) (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.