Gut hormone PYY(3-36) physiologically inhibits food intake.
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.
Batterham
Rachel L
RL
Imperial College Faculty of Medicine at Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Cowley
Michael A
MA
Small
Caroline J
CJ
Herzog
Herbert
H
Cohen
Mark A
MA
Dakin
Catherine L
CL
Wren
Alison M
AM
Brynes
Audrey E
AE
Low
Malcolm J
MJ
Ghatei
Mohammad A
MA
Cone
Roger D
RD
Bloom
Stephen R
SR
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
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