Gut Hormone PYY(3-36) Physiologically Inhibits Food Intake

Nature. 2002 Aug 8;418(6898):650-4. doi: 10.1038/nature00887.

Abstract

Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY(3-36) (PYY(3-36)), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY(3-36) in rats inhibits food intake and reduces weight gain. PYY(3-36) also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY(3-36) increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY(3-36) inhibits food intake. PYY(3-36) also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY(3-36) significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY(3-36) may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Appetite / drug effects*
  • Appetite / physiology
  • Arcuate Nucleus of Hypothalamus / cytology
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / physiology
  • Body Weight / drug effects
  • Electrophysiology
  • Energy Intake / drug effects
  • Feeding Behavior / drug effects*
  • Feeding Behavior / physiology
  • Gene Deletion
  • Humans
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Leptin / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / drug effects
  • Neurons / physiology
  • Peptide Fragments
  • Peptide YY / administration & dosage
  • Peptide YY / pharmacology*
  • Pro-Opiomelanocortin / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Neuropeptide Y / genetics
  • Receptors, Neuropeptide Y / metabolism
  • Signal Transduction / drug effects

Substances

  • Leptin
  • Peptide Fragments
  • Proto-Oncogene Proteins c-fos
  • Receptors, Neuropeptide Y
  • neuropeptide Y2 receptor
  • Peptide YY
  • peptide YY (3-36)
  • Pro-Opiomelanocortin