title: Exogenous peptide YY3-36 and Exendin-4 further decrease food intake, whereas octreotide increases food intake in rats after Roux-en-Y gastric bypass.
abstract: BACKGROUND
  Patients show an elevated postprandial satiety gut hormone release after Roux-en-Y Gastric bypass (gastric bypass). The altered gut hormone response appears to have a prominent role in the reduction of appetite and body weight (BW) after gastric bypass. Patients with insufficient BW loss after gastric bypass have an attenuated postprandial gut hormone response in comparison with patients who lost an adequate amount of BW. The effects of additional gut hormone administration after gastric bypass are unknown.
  
  
  METHODS
  The effects of peripheral administration of peptide YY3-36 (PYY3-36; 300 nmol kg(-1)), glucagon-like peptide-1 (GLP-1) analogue Exendin-4 (20 nmol kg(-1)) and somatostatin analogue octreotide (10 μg kg(-1)) on feeding and BW were evaluated in rats after gastric bypass.
  
  
  RESULTS
  Gastric bypass rats weighed (P<0.01) and ate less on postoperative day 5 (P<0.001) and thereafter, whereas postprandial plasma PYY and GLP-1 levels were higher compared with sham-operated controls (P<0.001). Administration of both PYY3-36 and Exendin-4 led to a further decrease in food intake in bypass rats compared with saline treatment (P=0.02 and P<0.0001, respectively). Similar reduction in food intake was observed in sham rats (P=0.02 and P<0.001, respectively). Exendin-4 treatment resulted in a significant BW loss in bypass (P=0.03) and sham rats (P=0.04). Subsequent treatment with octreotide led to an increase in food intake in bypass (P=0.007), but not in sham rats (P=0.87).
  
  
  CONCLUSIONS
  Peripheral administration of PYY3-36 and Exendin-4 reduces short-term food intake, whereas octreotide increases short-term food intake in rats after gastric bypass. The endogenous gut hormone response after gastric bypass can thus potentially be further enhanced by additional exogenous therapy with pharmacological doses of gut hormones in patients with insufficient weight loss or weight regain after surgery.
authors.affiliation: Department of Investigative Medicine, Imperial Weight Centre, Imperial College London, London, UK.
authors.forename: W K
authors.initials: WK
authors.lastname: Fenske
authors.forename: M
authors.initials: M
authors.lastname: Bueter
authors.forename: A D
authors.initials: AD
authors.lastname: Miras
authors.forename: M A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
authors.forename: C W
authors.initials: CW
authors.lastname: le Roux
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D001069:Appetite Regulation / Q000187:drug effects*; D019167:Appetite Stimulants / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D000077270:Exenatide; D015390:Gastric Bypass; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009765:Obesity / Q000188:drug therapy* / Q000601:surgery; D015282:Octreotide / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments; D019894:Peptide YY / Q000008:administration & dosage / Q000494:pharmacology*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D011184:Postoperative Period; D051381:Rats; D012527:Satiation; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001067:Appetite Depressants; D019167:Appetite Stimulants; D007004:Hypoglycemic Agents; D010446:Peptide Fragments; D010455:Peptides; D014688:Venoms; D019894:Peptide YY; C061785:peptide YY (3-36); D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D015282:Octreotide