Adiposome Lipidomic Shifts Following Bariatric Surgery in Association with Weight Loss and Cardiometabolic Benefit

Background Adiposomes carry bioactive lipids that shape systemic metabolism and vascular function. Building on our previous findings that obese adiposomes are ceramide/FFA-enriched and linked to dysfunction, we tested whether bariatric surgery remodels adiposome lipidomes and whether these shifts track with metabolic and vascular improvements. Methods Twenty-three obese individuals were assessed before and after bariatric surgery. Clinical evaluations included BMI, body composition, glycemic markers, inflammatory markers, and vascular function. Adipose tissue biopsies were collected, and adiposomes were isolated for non-targeted lipidomic analysis using mass spectrometry. Results Bariatric surgery induced significant reductions in BMI, visceral fat, HOMA-IR, inflammatory markers, and systolic blood pressure, alongside marked improvements in vascular function. Adiposome Lipidomics identified 550 species across 19 classes; 124 increased and 66 decreased post-surgery. Class-level shifts showed decreases in triglycerides, diglycerides, cholesteryl-esters, Phosphatidic-acids, fatty-acids, and acylcarnitines, with increases in phosphocholines, phosphoethanolamines, lysophosphatidylcholines, sphingomyelins, ultralong-chain Ceramides, and FAHFAs; these changes were larger in participants with ≥20% BMI reduction. Changes in 36 lipid species correlated with BMI change, e.g., TG 18:1/20:4/22:6 positively, whereas SM d40:1, SM d42:4, and PC 17:0/18:2 inversely. Improvements in nitric oxide, vascular reactivity, and adiponectin tracked with rises in ultralong-chain Cer/FAHFAs/phospholipids and declines in ACar/CE/DG/PA. Machine learning models predicted BMI from lipid features with >80% accuracy (R² > 0.90; MAE < 0.3), highlighting SM d40:1, SM d42:4, and FA 17:1 as top contributors. Pathway enrichment analysis linked these changes to sphingolipid signaling and glycerophospholipid metabolism. Conclusion Bariatric surgery remodels adiposome lipids, and these shifts align with improvements in cardiometabolic risk markers