title: Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery.
abstract: 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 PYY3-36and (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 PYY3-36increased 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.
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M S
authors.initials: MS
authors.lastname: Svane
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: N B
authors.initials: NB
authors.lastname: Jørgensen
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: K N
authors.initials: KN
authors.lastname: Bojsen-Møller
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Dirksen
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Nielsen
authors.affiliation: Department of Surgical Gastroenterology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: V B
authors.initials: VB
authors.lastname: Kristiansen
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.|Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Toräng
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.|Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: N J
authors.initials: NJ
authors.lastname: Wewer Albrechtsen
authors.affiliation: Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: J F
authors.initials: JF
authors.lastname: Rehfeld
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.|Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Madsbad
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.|Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
mesh_terms: D001066:Appetite / Q000502:physiology; D001069:Appetite Regulation / Q000502:physiology*; D018592:Cross-Over Studies; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000517:prevention & control; D004435:Eating / Q000502:physiology*; D005260:Female; D015390:Gastric Bypass; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D009767:Obesity, Morbid / Q000097:blood / Q000601:surgery*; D010446:Peptide Fragments / Q000627:therapeutic use; D019894:Peptide YY / Q000097:blood / Q000378:metabolism*; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D019894:Peptide YY; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1