Abstract 12543: Glucagon-Like Peptide-1 Improves Endothelial and HDL Function Immediately after Roux-en-Y Gastric Bypass Prior to Body Weight Loss
Background: Roux-en-Y gastric bypass (RYGB) reduces weight and long-term cardiovascular (CV) risk in obese patients. Glucagon-like peptide-1 (GLP-1) levels increase after RYGB and seem to mediate several beneficial RYGB effects, partly in a weight-independent manner. GLP-1 exerts endothelial protective actions through endothelial-NO-synthase (eNOS) activation. Here, we investigated the role of GLP-1 in the improvement of obesity-induced endothelial and HDL dysfunction in rats after RYGB, prior to significant weight loss.
Methods: Diet-induced obese male Wistar rats underwent RYGB and received for 8 days vehicle (RYv) or GLP-1 receptor antagonist exendin (9-39) (RY-Exe); they were compared to sham-operated rats fed ad lib (AL) treated for 8 days with vehicle (ALv) or GLP-1 agonist liraglutide (AL-lira). Cumulative relaxation responses of the thoracic aorta were performed to peptide GLP-1 (7[[Unable to Display Character: –]]36) amide (10-12 to 10-6mol/L) after submaximal contraction with norepinephrine (10-6mol/L) and repeated after pre-incubation with eNOS-inhibitor (L-NAME, 10-4mol/L). HDL reverse cholesterol transport (RCT) capacity was measured ex vivo incubating J774 macrophages with apolipoprotein B-depleted rat serum.
Results: 8 days post-surgery, body weight among the 4 groups did not yet differ significantly. GLP-1-induced vasorelaxation was impaired in sham ALv compared to RYv rats (max relaxations: 28.8±3.6 % and 37±2.3%, respectively, n=6-8, p≤0.05). L-NAME inhibited GLP-1-induced vasodilation, suggesting eNOS activation. AL[[Unable to Display Character: –]]lira rats had preserved vasorelaxation that was not different from RYv; in contrast, chronic exendin 9 blunted the improved vasorelaxation in RYGB rats. Interestingly, HDL RCT capacity was similarly improved in both RYv and AL-lira treated rats compared to ALv, but it was impaired in RYGB receiving Exendin 9.
Conclusions: Our study shows that GLP-1 may be a crucial mediator of the improved endothelial and HDL function that is observed immediately after RYGB, indicating a new potential mechanism for the CV protective effects of RYGB, in addition to weight loss.
- © 2013 by American Heart Association, Inc.