Abstract 14621: High-Density Lipoprotein Lipid and Protein Cargo and Cholesterol Efflux Capacity Before and After Bariatric Surgery

Introduction: Cholesterol efflux capacity (CEC) is inversely associated with incident CV events, independent of HDL-C. Obesity is characterized by low HDL-C and impaired HDL function. Bariatric surgery, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), improves CV risk, but we have shown that the impact on CEC may differ by procedure over time post-op.

Hypothesis: We hypothesized that RYGB and SG significantly affect HDL protein/lipid cargo and mediate CEC.

Methods: We prospectively studied severely obese, nondiabetic women undergoing RYGB (n=31) or SG (n=36) before and at 6 and 12 months after surgery. Statistical analyses included Wilcoxon tests of log fold change in HDL proteins/lipids, hierarchical clustering to identify HDL protein/lipid clusters, and network mediation tests to identify cargo associated with CEC changes.

Results: Subjects experienced similar weight loss regardless of procedure (38.0±10.4 kg at 12mo). Concentrations of 40 proteins (11 up, 29 down) and 95 lipids (46 up, 49 down) in HDL changed significantly following bariatric surgery. Proteins and lipids clustered into 9 and 14 groups of similar post-operative trajectories, respectively (Figure A). All clusters, other than 2 lipid clusters, showed similar responses regardless of procedure (Figure B). Despite similarities in cargo, changes in CEC differed depending upon time point and efflux pathway (Figure C). Network mediation analyses suggested that changes in 4 protein and 2 lipid clusters associated with post-operative changes in ABCA1-mediated CEC and changes in 1 lipid cluster associated with changes in non-ABCA1-mediated CEC (Figure D).

Conclusions: In conjunction with substantial weight loss, bariatric surgery results in altered HDL protein/lipid cargo and CEC, possibly mediated by distinct HDL cargo. Further study of the mechanisms influencing HDL cargo in obesity and after bariatric surgery may lead to better understanding of CEC and management of CVD.