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

M S Svane; Nils B Jørgensen; K N Bojsen-Møller; C Dirksen; S. Nielsen; V B Kristiansen; S Toräng; N J Wewer Albrechtsen; J F Rehfeld; B Hartmann; S Madsbad; J J Holst

doi:10.1038/ijo.2016.121

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

M S Svane, Nils B Jørgensen, K N Bojsen-Møller, C Dirksen, S. Nielsen, V B Kristiansen, S Toräng, N J Wewer Albrechtsen, J F Rehfeld, B Hartmann, S Madsbad, J J Holst

Institut for Klinisk Medicin

99 Citationer (Scopus)

Abstract

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 PYY 3-36.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 PYY 3-36 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 PYY 3-36 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 PYY 3-36, 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.

Originalsprog	Engelsk
Tidsskrift	International Journal of Obesity
Vol/bind	40
Sider (fra-til)	1699–1706
ISSN	0307-0565
DOI	https://doi.org/10.1038/ijo.2016.121
Status	Udgivet - 1 nov. 2016

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10.1038/ijo.2016.121

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Svane, M. S., Jørgensen, N. B., Bojsen-Møller, K. N., Dirksen, C., Nielsen, S., Kristiansen, V. B., Toräng, S., Wewer Albrechtsen, N. J., Rehfeld, J. F., Hartmann, B., Madsbad, S., & Holst, J. J. (2016). Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery. International Journal of Obesity, 40, 1699–1706. https://doi.org/10.1038/ijo.2016.121

Svane, MS, Jørgensen, NB, Bojsen-Møller, KN, Dirksen, C, Nielsen, S, Kristiansen, VB, Toräng, S, Wewer Albrechtsen, NJ , Rehfeld, JF , Hartmann, B , Madsbad, S & Holst, JJ 2016, 'Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery', International Journal of Obesity, bind 40, s. 1699–1706. https://doi.org/10.1038/ijo.2016.121

@article{126632088629454c920bd9eeeca9e445,

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

abstract = "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 PYY 3-36.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 PYY 3-36 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 PYY 3-36 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 PYY 3-36, 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.",

author = "Svane, {M S} and J{\o}rgensen, {Nils B} and Bojsen-M{\o}ller, {K N} and C Dirksen and S. Nielsen and Kristiansen, {V B} and S Tor{\"a}ng and {Wewer Albrechtsen}, {N J} and Rehfeld, {J F} and B Hartmann and S Madsbad and Holst, {J J}",

year = "2016",

month = nov,

day = "1",

doi = "10.1038/ijo.2016.121",

language = "English",

volume = "40",

pages = "1699–1706",

journal = "International Journal of Obesity",

issn = "0307-0565",

publisher = "nature publishing group",

}

TY - JOUR

T1 - Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery

AU - Svane, M S

AU - Jørgensen, Nils B

AU - Bojsen-Møller, K N

AU - Dirksen, C

AU - Nielsen, S.

AU - Kristiansen, V B

AU - Toräng, S

AU - Wewer Albrechtsen, N J

AU - Rehfeld, J F

AU - Hartmann, B

AU - Madsbad, S

AU - Holst, J J

PY - 2016/11/1

Y1 - 2016/11/1

N2 - 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 PYY 3-36.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 PYY 3-36 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 PYY 3-36 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 PYY 3-36, 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.

AB - 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 PYY 3-36.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 PYY 3-36 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 PYY 3-36 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 PYY 3-36, 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.

U2 - 10.1038/ijo.2016.121

DO - 10.1038/ijo.2016.121

M3 - Journal article

C2 - 27434221

SN - 0307-0565

VL - 40

SP - 1699

EP - 1706

JO - International Journal of Obesity

JF - International Journal of Obesity

ER -

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

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