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

Int J Obes (Lond). 2016 Nov;40(11):1699-1706. doi: 10.1038/ijo.2016.121. Epub 2016 Aug 30.


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), whereas PYY actions can be inhibited by the 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 months after RYGB with and without Ex-9. In study 2, 12 RYGB-operated patients were examined in a randomized, placebo-controlled, crossover 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, whereas 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, whereas neither GLP-1 receptor blockage nor DPP-4 inhibition alone affected food intake, perhaps because of 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 have a role in decreased food intake postoperatively.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Appetite / physiology
  • Appetite Regulation / physiology*
  • Cross-Over Studies
  • Denmark
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / prevention & control
  • Eating / physiology*
  • Female
  • Gastric Bypass*
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide-1 Receptor / antagonists & inhibitors
  • Humans
  • Male
  • Obesity, Morbid / blood
  • Obesity, Morbid / surgery*
  • Peptide Fragments / therapeutic use
  • Peptide YY / blood
  • Peptide YY / metabolism*
  • Treatment Outcome
  • Weight Loss


  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Peptide YY
  • exendin (9-39)
  • Glucagon-Like Peptide 1