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

Abstract

Adiposomes carry bioactive lipids that shape systemic metabolism and vascular function. Building on our previous findings that obese adiposomes are ceramide/free fatty acid-enriched and linked to dysfunction, we tested whether bariatric surgery remodels adiposome lipidomes and whether these shifts track with metabolic and vascular improvements. Twenty-three obese individuals were assessed before and after bariatric surgery. Clinical evaluations included body mass index (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. 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 after 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 fatty acid-hydroxy fatty acids (FAHFAs); these changes were larger in participants with ≥20% BMI reduction. Changes in 36 lipid species correlated with BMI change: triglycerides 18:1/20:4/22:6 positively, and sphingomyelins (SM) d40:1, SM d42:4, and phosphatidylcholine 17:0/18:2 inversely. Improvements in nitric oxide, vascular reactivity, and adiponectin tracked with rises in ultralong-chain ceramide/FAHFAs/phospholipids and declines in acylcarnitine/cholesterol esters/diacylglycerols/phosphatidic acids. Machine learning models predicted BMI from lipid features with >80% accuracy (R2 >0.90; mean absolute error <0.3), highlighting SM d40:1, SM d42:4, and fatty acid 17:1 as top contributors. Pathway enrichment analysis linked these changes to sphingolipid signaling and glycerophospholipid metabolism. Bariatric surgery remodels adiposome lipids, and these shifts align with improvements in cardiometabolic risk markers.