Exogenous peptide YY3-36 and Exendin-4 further decrease food intake, whereas octreotide increases food intake in rats after Roux-en-Y gastric bypass

Abstract

Background: Patients show an elevated postprandial satiety gut hormone release after Roux-en-Y Gastric bypass (gastric bypass). The altered gut hormone response appears to have a prominent role in the reduction of appetite and body weight (BW) after gastric bypass. Patients with insufficient BW loss after gastric bypass have an attenuated postprandial gut hormone response in comparison with patients who lost an adequate amount of BW. The effects of additional gut hormone administration after gastric bypass are unknown. Methods: The effects of peripheral administration of peptide YY3-36 (PYY3-36; 300 nmol kg À1 ), glucagon-like peptide-1 (GLP-1) analogue Exendin-4 (20 nmol kg À1 ) and somatostatin analogue octreotide (10 mg kg À1 ) on feeding and BW were evaluated in rats after gastric bypass. Results: Gastric bypass rats weighed (Po0.01) and ate less on postoperative day 5 (Po0.001) and thereafter, whereas postprandial plasma PYY and GLP-1 levels were higher compared with sham-operated controls (Po0.001). Administration of both PYY3-36 and Exendin-4 led to a further decrease in food intake in bypass rats compared with saline treatment (P ¼ 0.02 and Po0.0001, respectively). Similar reduction in food intake was observed in sham rats (P ¼ 0.02 and Po0.001, respectively). Exendin-4 treatment resulted in a significant BW loss in bypass (P ¼ 0.03) and sham rats (P ¼ 0.04). Subsequent treatment with octreotide led to an increase in food intake in bypass (P ¼ 0.007), but not in sham rats (P ¼ 0.87). Conclusion: Peripheral administration of PYY3-36 and Exendin-4 reduces short-term food intake, whereas octreotide increases short-term food intake in rats after gastric bypass. The endogenous gut hormone response after gastric bypass can thus potentially be further enhanced by additional exogenous therapy with pharmacological doses of gut hormones in patients with insufficient weight loss or weight regain after surgery.

Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

“…Furthermore, inhibition of gut hormone responses, including the PYY response with the somatostatin analog octreotide in patients who had undergone RYBGP, results in increased hunger and increased food intake (60). In a rat model of RGYBP, blockade of endogenous PYY resulted in increased food intake (75). Additionally administration of the GLP-1R antagonist exendin(9-39) increased food intake but did not alter energy expenditure after RYGBP (76).…”

The role of bariatric surgery in the treatment of diabetes

“…In patients with longstanding T2DM who may require increasing doses of exogenous insulin, surgery may allow the patient to come off all insulin or facilitate a significant dose reduction and simplification of the regimen from basal bolus to only requiring once daily insulin analogue therapy [Fenske et al 2012].…”

GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents

“…Strong indirect evidence comes from studies in RYGB patients, with appetite and body weight negatively correlated with elevated PYY and GLP-1 concentrations (38). Furthermore, food intake increased upon treatment of RYGB patients (38) and rats after RYGB (22) with the nonspecific inhibitor of gut hormone secretion octreotide. There have been only two attempts to mechanistically and directly test the role of endogenous GLP-1 and PYY in the weight-reducing effects of bariatric surgeries.…”