Selective beneficial cardiometabolic effects of vertical sleeve gastrectomy are predominantly mediated through glucagon-like peptide (GLP-1) in Zucker diabetic fatty rats

BACKGROUND: Glucagon-like peptide-1 (GLP-1) level was significantly increased post Vertical Sleeve Gastrectomy (VSG), an effect believed to contribute to its beneficial cardiometabolic effects. OBJECTIVE: To validate the beneficial GLP-1 mediated cardiometabolic effects post VSG using GLP-1 antagonist (exendin 9-39) in Zucker diabetic fatty rats. METHODS: Animals were divided into three (n = 5) groups: (i) sham, (ii) VSG, and (iii) VSG received exendin 9–39 (GLP-1 receptor antagonist). The study was performed over 12 weeks and parameters were measured 12 weeks post-surgery. RESULTS AND DISCUSSION: As expected, fasting blood glucose and insulin levels were improved post VSG due to enhanced GLP-1 secretion. However, both fasting glucose and insulin levels were impaired in the presence of GLP-1 antagonist. Baseline total cholesterol level pre-surgery was 100±1 mg/dl which remained unchanged in the VSG group but significantly increased to 140±8 mg/dl in the presence of antagonist. Interestingly, post-surgery there was a nearly 70% reduction in triglyceride level in the VSG group compared to sham which was overcome in the presence of antagonist. Myographic studies using aortic rings showed no significant change between groups. Additionally, blood pressure and heart rate also remained unchanged in all groups. Serum bile acid and L-PGDS levels increased post VSG but significantly decreased in the presence of antagonist, suggesting a strong association with GLP-1 and a novel mechanism of action. CONCLUSION: Enhanced GLP-1 secretion post VSG imparted beneficial cardiometabolic effects on blood glucose, insulin, total cholesterol, triglyceride, bile acids and L-PGDS levels which were abated in the presence of GLP-1 antagonist.