Acute peripheral GLP-1 receptor agonism or antagonism does not alter energy expenditure in rats after Roux-en-Y gastric bypass

• Compensatory fall in energy expenditure after weight loss is attenuated by RYGB.
• Acute injection of GLP-1 antagonist Exendin-9 increases eating only in RYGB rats.
• Enhanced release of GLP-1 may contribute to inhibitory effect of RYGB on eating.
• Acute administration of GLP-1 agonist Exendin-4 decreases eating more in RYGB rats.
• Acute modulation of GLP-1 signaling does not alter energy expenditure in RYGB rats.

Compared to traditional weight loss strategies, the compensatory decrease in energy expenditure in response to body weight loss is markedly attenuated after Roux-en-Y gastric bypass surgery (RYGB). Because basal and postprandial levels of glucagon-like peptide-1 (GLP-1) are increased after RYGB surgery, and because GLP-1 has been shown to increase energy expenditure, we investigated if increased GLP-1 levels are involved in the alterations in energy expenditure after RYGB. Adult male Wistar rats were randomized for RYGB (n = 8) or sham surgery (n = 17). Part of the sham-operated rats were food restricted and body weight-matched (n = 8) to the RYGB animals. The effects of acute subcutaneous administration of the GLP-1 antagonist Exendin (9–39) (Ex-9, 30 μg/kg) or the GLP-1 agonist Exendin-4 (Ex-4, 5 μg/kg), respectively, on energy expenditure were tested using indirect calorimetry. We found that Ex-9 increased food intake in RYGB, but not in sham-operated rats.Energy expenditure was lower in RYGB and sham-operated body weight-matched rats compared to sham-operated ad libitum fed rats, but significantly higher in RYGB rats compared to sham-operated body weight-matched rats. There was no effect of Ex-9 treatment on energy expenditure in either group of animals. Similarly, Ex-4 decreased food intake more in RYGB than in sham-operated rats, but Ex-4 did not modulate energy expenditure in any surgical group. We conclude that acute modulation of GLP-1 signaling is not directly involved in altered energy expenditure after RYGB surgery in rats.