title: Gut hormone PYY(3-36) physiologically inhibits food intake.
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.
authors.affiliation: Imperial College Faculty of Medicine at Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Batterham
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cowley
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Small
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.forename: Mark A
authors.initials: MA
authors.lastname: Cohen
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Dakin
authors.forename: Alison M
authors.initials: AM
authors.lastname: Wren
authors.forename: Audrey E
authors.initials: AE
authors.lastname: Brynes
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Low
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: Roger D
authors.initials: RD
authors.lastname: Cone
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001066:Appetite / Q000187:drug effects* / Q000502:physiology; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D004594:Electrophysiology; D002149:Energy Intake / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D017353:Gene Deletion; D006801:Humans; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments; D019894:Peptide YY / Q000008:administration & dosage / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020738:Leptin; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D019894:Peptide YY; C061785:peptide YY (3-36); D011333:Pro-Opiomelanocortin