title: Gastric bypass surgery reduces plasma ceramide subspecies and improves insulin sensitivity in severely obese patients.
abstract: 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.
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Hazel
authors.initials: H
authors.lastname: Huang
authors.forename: Takhar
authors.initials: T
authors.lastname: Kasumov
authors.forename: Patrick
authors.initials: P
authors.lastname: Gatmaitan
authors.forename: Helen M
authors.initials: HM
authors.lastname: Heneghan
authors.forename: Sangeeta R
authors.initials: SR
authors.lastname: Kashyap
authors.forename: Philip R
authors.initials: PR
authors.lastname: Schauer
authors.forename: Stacy A
authors.initials: SA
authors.lastname: Brethauer
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
mesh_terms: D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000209:etiology / Q000473:pathology; D002518:Ceramides / Q000097:blood*; D005227:Fatty Acids / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D015390:Gastric Bypass / Q000379:methods*; D006801:Humans; D007333:Insulin Resistance; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000601:surgery*; D011182:Postoperative Care; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D002518:Ceramides; D005227:Fatty Acids; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha