Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery.

BACKGROUND/OBJECTIVES: Exaggerated postprandial secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) may explain appetite reduction and weight loss after Roux-en-Y gastric bypass (RYGB), but causality has not been established. We hypothesized that food intake decreases after surgery through combined actions from GLP-1 and PYY. GLP-1 actions can be blocked using the GLP-1 receptor antagonist Exendin 9-39 (Ex-9), while PYY actions can be inhibited by administration of a dipeptidyl peptidase-4 (DPP-4) inhibitor preventing the formation of PYY3-36.

SUBJECTS/METHODS: Appetite regulating gut-hormones and appetite ratings during a standard mixed-meal test and effects on subsequent ad libitum food intake were evaluated in two studies: In study 1, nine patients with type 2 diabetes were examined prospectively before and 3 month after RYGB with and without Ex-9. In study 2, 12 RYGB-operated patients were examined in a randomized, placebo-controlled, cross-over design on four experimental days with: 1) placebo, 2) Ex-9, 3) the DPP-4 inhibitor, sitagliptin, to reduce formation of PYY3-36 and 4) Ex-9/sitagliptin combined.

RESULTS: In study 1, food intake decreased by 35% following RYGB compared with before surgery. Before surgery, GLP-1 receptor blockage increased food intake but no effect was seen postoperatively, while PYY secretion was markedly increased. In study 2, combined GLP-1 receptor blockage and DPP-4 inhibitor mediated lowering of PYY3-36 increased food intake by ~20% in RYGB patients, while neither GLP-1 receptor blockage nor DPP-4 inhibition alone affected food intake, perhaps due to concomitant marked increases in the unblocked hormone.

CONCLUSIONS: Blockade of actions from only one of the two L-cell hormones, GLP-1 and PYY3-36, resulted in concomitant increased secretion of the other, probably explaining the absent effect on food intake on these experimental days. Combined blockade of GLP-1 and PYY-actions increased food intake after RYGB, supporting that these hormones play a role in decreased food intake postoperatively.International Journal of Obesity accepted article preview online, 19 July 2016. doi:10.1038/ijo.2016.121.