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Clinical Studies and Practice

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



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.


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.


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.


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.

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We are indebted to the patients for their willingness to participate in the study and are grateful for technical assistance to Alis Andersen and Sussi Polmann (Department of Endocrinolgy, Copenhagen University Hospital Hvidovre, Denmark), and Lene Albak and Lone Bagger Thielsen (Department of Biomedical Sciences, Panum Institute, University of Copenhagen, København, Denmark). MSS has a PhD scholarship funded by the University of Copenhagen and KNBM has a postdoc funded by the Danish Council for Independent Research, Denmark (DFF—4092-00218). Further funding was received from Copenhagen University Hospital Hvidovre, Denmark and the Danish Medical Association, Denmark.

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Correspondence to J J Holst.

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MSS, NBJ, KNBM, CD, ST, NJWA, JJH and SM are affiliated by the Novo Nordisk Foundation Center for Basic Metabolic Research, which is funded by the Novo Nordisk Foundation. NBJ had 1/3 of his PhD scholarship funded by Novo Nordisk A/S. The other authors declare no relevant conflict of interest.

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Svane, M., Jørgensen, N., Bojsen-Møller, K. et al. Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery. Int J Obes 40, 1699–1706 (2016).

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