E. Osto1, A. Jomard1, P. Doytcheva1, O. Chavez-Talavera2, A. Tailleux2, B. Staels2, A. von Eckardstein1, C. Wolfrum3, F. Ruschitzka4, T. Lutz4 (1Schlieren-Zurich ; 2Lille FR; 3Schwerzenbach ; 4Zurich)
Background: Bariatric surgery (RYGB) reduces cardiovascular mortality and improves HDL mediated vasoprotection. Bile acids (BA) are emerging as signaling molecules controlling cardio-metabolic health. Plasmatic BA circulate partly bound to HDL. Purpose: we tested whether and how changes in composition of BA bound to HDL (HDL-BA) after RYGB contribute to HDL-mediated endothelial protection. Methods: HDL isolated from 47 obese patients before and 1 year after RYGB were tested for their protective properties using human endothelial cell in vitro. HDL BA and lipid composition was quantified by liquid chromatography-mass spectrometry (LC/MS). Results: 1 year after RYGB, higher concentrations (up to 25%) of BA were bound to HDL with an increase on HDL of BA agonists either for nuclear FXR, e.g. cholic acid (CA) and chenodeoxy-CA (CDCA), or for membrane receptor TGR5, e.g. taurolitho-CA (TLCA). After RYGB, HDL levels were increased and HDL-mediated endothelial NO production, anti-apoptotic and cholesterol efflux capacity were restored. The composition-function analysis showed that higher HDL-CA correlated with improved anti-apoptotic capacity. Further, RYGB improves the lipidomic profile of HDL with reduced cholesteryl esters and toxic ceramides, and increased anti-oxidant plasmalogens.
Conclusions: RYGB increases the concentration and improves the function and the molecular lipid composition of HDL. Interestingly, higher concentrations of BA bound to HDL after RYGB may mediate HDL’s improved endothelial-protective effects via enhanced endothelial activation of FXR and TGR5.