Changes in Plasma Sphingolipid Metabolites Following Roux‐En‐Y Gastric Bypass in Women With Obesity and Type 2 Diabetes: A Pilot Metabolomic Cohort Study

Although sphingolipids are key players in lipotoxicity and metabolic diseases, their response to bariatric surgery and their relation to metabolic improvement remain unclear. This pilot study investigated plasma sphingolipid remodeling after Roux-en-Y gastric bypass (RYGB) and its associations with clinical and biochemical markers of postoperative metabolic improvement in women with obesity and type 2 diabetes (T2DM). Plasma samples, anthropometric, body composition, and biochemical data (glucose, HbA1c, insulin, C-peptide, and lipid profile) were collected from 30 participants before and 3 months after surgery. T2DM remission was defined according to ADA 2021 criteria. Plasma sphingolipids were identified using untargeted metabolomics, which involved ultra-performance liquid chromatography coupled with mass spectrometry. Univariate and multivariate analyses were performed using Jamovi (version 2.2.5) and MetaboAnalyst (versions 5.0 and 6.0). RYGB led to reductions in body weight and anthropometric measures, with improved body composition. Patients demonstrated glycemic improvement, with 18 achieving remission of T2DM. The lipid profile also improved, with a decline in total cholesterol driven by reductions in pro-atherogenic fractions. Among 32 plasma sphingolipids identified, 21 changed significantly after surgery. Sphingolipids showed strong-to-robust correlations with the lipid profile, particularly SM(d18:1/20:0) and SM(d18:1/22:0) with total cholesterol and LDL-c after surgery, but moderate and poor correlations with body composition, and glycemic markers, respectively. Plasma sphingolipids underwent significant remodeling after RYGB, with strong associations with plasma cholesterol, particularly with SM(d18:1/20:0) and SM(d18:1/22:0). These findings suggest that specific sphingolipid species may contribute to or reflect plasma lipid adaptations to surgery and warrant further investigation as potential metabolic biomarkers. Trial Registration: This protocol is part of a broader umbrella study registered at www.clinicaltrials.gov under the identifier NCT01251016.