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/m²) 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.