Peptide YY3-36 and glucagon-like peptide-17-36 inhibit food intake additively

Endocrinology. 2005 Dec;146(12):5120-7. doi: 10.1210/en.2005-0237. Epub 2005 Sep 8.


Peptide YY (PYY) and glucagon like peptide (GLP)-1 are cosecreted from intestinal L cells, and plasma levels of both hormones rise after a meal. Peripheral administration of PYY(3-36) and GLP-1(7-36) inhibit food intake when administered alone. However, their combined effects on appetite are unknown. We studied the effects of peripheral coadministration of PYY(3-36) with GLP-1(7-36) in rodents and man. Whereas high-dose PYY(3-36) (100 nmol/kg) and high-dose GLP-1(7-36) (100 nmol/kg) inhibited feeding individually, their combination led to significantly greater feeding inhibition. Additive inhibition of feeding was also observed in the genetic obese models, ob/ob and db/db mice. At low doses of PYY(3-36) (1 nmol/kg) and GLP-1(7-36) (10 nmol/kg), which alone had no effect on food intake, coadministration led to significant reduction in food intake. To investigate potential mechanisms, c-fos immunoreactivity was quantified in the hypothalamus and brain stem. In the hypothalamic arcuate nucleus, no changes were observed after low-dose PYY(3-36) or GLP-1(7-36) individually, but there were significantly more fos-positive neurons after coadministration. In contrast, there was no evidence of additive fos-stimulation in the brain stem. Finally, we coadministered PYY(3-36) and GLP-1(7-36) in man. Ten lean fasted volunteers received 120-min infusions of saline, GLP-1(7-36) (0.4 pmol/kg.min), PYY(3-36) (0.4 pmol/kg.min), and PYY(3-36) (0.4 pmol/kg.min) + GLP-1(7-36) (0.4 pmol/kg.min) on four separate days. Energy intake from a buffet meal after combined PYY(3-36) + GLP-1(7-36) treatment was reduced by 27% and was significantly lower than that after either treatment alone. Thus, PYY(3-36) and GLP-1(7-36), cosecreted after a meal, may inhibit food intake additively.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / physiopathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Combinations
  • Drug Synergism
  • Eating / drug effects*
  • Energy Intake / drug effects
  • Feeding Behavior / drug effects
  • Female
  • Glucagon / administration & dosage
  • Glucagon / pharmacology*
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides / administration & dosage
  • Glucagon-Like Peptides / pharmacology*
  • Humans
  • Immunohistochemistry
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Obesity / genetics
  • Obesity / physiopathology
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Peptide YY / administration & dosage
  • Peptide YY / pharmacology*
  • Rats


  • Drug Combinations
  • Peptide Fragments
  • Peptide YY
  • glucagon-like peptide 1 (7-36)
  • peptide YY (3-36)
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon