Author + information
- Elena Osto,
- Caroline Corteville,
- Kerstin Spliethoff,
- Marco Bueter,
- Christian Matter,
- Thomas Lutz and
- Thomas F. Luscher
Roux–en–Y gastric bypass (RYGB) reduces weight and cardiovascular (CV) risk in obese patients. The mechanisms of CV protection after RYGB are still unclear but may be partly weight–independent. Glucagon like peptide–1 (GLP–1) exerts endothelial protective actions through endothelial–NO–synthase (eNOS) activation. Here, we investigated the role of GLP–1 in obesity–induced endothelial dysfunction in rats after RYBG prior to significant weight loss.
After 7 weeks on a high–fat high–cholesterol diet, male Wistar rats underwent RYGB or sham surgery. Sham rats were fed ad lib (AL) or body weight–matched (BWM) to RYGB. Thoracic aortic rings were collected 8 days post–surgery and suspended for isometric tension recording. Cumulative relaxation responses were performed to peptide GLP–1 (7–36) amide (10–12 to 10–6mol/L) after submaximal contraction with norepinephrine (10–6mol/L), and after preincubation with the GLP–1 antagonist exendin (9–39) (10–7 mol/L) or the eNOS–inhibitor L–NAME (10–4mol/L). Western blot of aortic lysates using GLP–1 receptor and eNOS antibodies was performed to address the role of GLP–1 signaling in endothelial function. Fasting plasma GLP–1 was measured.
On day 8 post–surgery, the weight difference among the 3 groups was not yet significant. GLP–1–induced vasorelaxation was impaired in sham AL and BWM compared with RYGB rats (max relaxations: 17±3.1 % vs 15±2.8 vs 36±4.8, resp., n=6–8, p<0.05). Exendin (9–39) and L–NAME inhibited GLP–1–induced vasodilation, suggesting a mechanism requiring GLP–1 receptor and eNOS activation. GLP–1 receptor protein expression was lower in aortic lysates from sham AL and BWM compared to RYGB (0.44±0.1 vs 0.49±0.1 vs 0.86±0.2 relative units, p<0.05); eNOS expression was also reduced (0.45±0.1 vs 0.34±0.1 vs 0.74±0.1). Plasma fasting levels of GLP–1 were increased in rats after RYGB compared to sham AL and BWM (0.8±0.1 vs 2.0±0.9 vs 10±2.8 pg/ml, p<0.05).
Our study suggests that GLP–1 may be a crucial mediator of the endothelial function improvement observed immediately after RYGB, indicating a new potential mechanism for the CV protective effects of RYGB, in addition to weight loss.
Poster Sessions, Expo North
Sunday, March 10, 2013, 9:45 a.m.–10:30 a.m.
Session Title: Spotlight on the Endothelium
Abstract Category: 33. Vascular Medicine: Basic
Presentation Number: 1211–168
- 2013 American College of Cardiology Foundation