Preoperative Cer(d18:1/24:0) Shows Promise as a Candidate Predictor of Plasma Lipid Phenotypes Following Roux-en-Y Gastric Bypass in Women: An Exploratory Analysis of the SURMetaGIT Study.

Roux-en-Y gastric bypass (RYGB) surgery is known to improve lipid profiles in individuals with obesity, but the degree of improvement varies. Emerging evidence suggests a role for sphingolipids in modulating cholesterol metabolism. This study investigated the relationship between plasma sphingolipid changes and cholesterol improvements in women with obesity and Type 2 diabetes mellitus (T2DM) following RYGB. Patients from the SURMetaGIT study were evaluated before and 3 months after surgery. Biochemical and sphingolipid analyses, anthropometric measures, and body composition were assessed. A nonhierarchical cluster analysis assessed distinct phenotypes in response to cholesterol after surgery. The p value from multiple comparison tests was adjusted using the false discovery rate (FDR) method. A metabolite fold change [log2 (postoperative mean/preoperative mean)] of 1.2 and an adjusted p value < 5% were considered statistically significant. A linear regression model was used to investigate the relationship between sphingolipids and cholesterol levels. Finally, a binary logistic regression model was developed to identify the predictive value of specific discriminative sphingolipids in the lipid improvement after RYGB. Distinct sphingolipid remodeling patterns were observed, with specific sphingolipids, including Cer(d18:1/24:0), SM(d18:1/22:0), and SM(d18:1/24:0), presenting a strong positive correlation with cholesterol levels, independent of weight loss and T2DM remission. The binary logistic regression showed preoperative Cer(d18:1/24:0) could be the strongest candidate predictor of plasma lipid improvement after surgery (accuracy of 78%; AUC 0.87). These findings suggest that specific sphingolipids, notably preoperative Cer(d18:1/24:0), seemed to have a potential role in predicting cholesterol improvement after RYGB. External validation in independent cohorts is warranted before clinical applicability can be established. Trial Registration: ClinicalTrials.gov identifier: NCT01251016.