PYY3-36 injection in mice produces an acute anorexigenic effect followed by a delayed orexigenic effect not observed with other anorexigenic gut hormones.
Peptide YY (PYY) is secreted postprandially from the endocrine L cells of the gastrointestinal tract. PYY(3-36), the major circulating form of the peptide, is thought to reduce food intake in humans and rodents via high-affinity binding to the autoinhibitory neuropeptide Y (NPY) receptor within the arcuate nucleus. We studied the effect of early light-phase injection of PYY(3-36) on food intake in mice fasted for 0, 6, 12, 18, 24, and 30 h and show that PYY(3-36) produces an acute anorexigenic effect regardless of the duration of fasting. We also show evidence of a delayed orexigenic effect in ad libitum-fed mice injected with PYY(3-36) in the early light phase. This delayed orexigenic effect also occurs in mice administered a potent analog of PYY(3-36), d-Allo Ile(3) PYY(3-36), but not following injection of other anorectic agents (glucagon-like-peptide 1, oxyntomodulin, and lithium chloride). Early light-phase injection of PYY(3-36) to ad libitum-fed mice resulted in a trend toward increased levels of hypothalamic NPY and agouti-related peptide mRNA and a decrease in proopiomelanocortin mRNA at the beginning of the dark phase. Furthermore, plasma levels of ghrelin were increased significantly, and there was a trend toward decreased plasma PYY(3-36) levels at the beginning of the dark phase. These data indicate that PYY(3-36) injection results in an acute anorexigenic effect followed by a delayed orexigenic effect.
Parkinson
James R C
JR
Department of Metabolic Medicine, Hammersmith Hospital, Imperial College London, Du Cane Road, London, W12 ONN UK.
Dhillo
Waljit S
WS
Small
Caroline J
CJ
Chaudhri
Owais B
OB
Bewick
Gavin A
GA
Pritchard
Iain
I
Moore
Stanley
S
Ghatei
Mohammed A
MA
Bloom
Stephen R
SR
D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D001067:Appetite Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005215:Fasting; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D054795:Incretins / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D053772:Oxyntomodulin / Q000494:pharmacology; D010446:Peptide Fragments; D019894:Peptide YY / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012528:Satiety Response / Q000187:drug effects*; D013047:Specific Pathogen-Free Organisms
D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D018692:Antimanic Agents; D001067:Appetite Depressants; D054795:Incretins; D047908:Intracellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D053772:Oxyntomodulin; D010446:Peptide Fragments; D012333:RNA, Messenger; D019894:Peptide YY; C061785:peptide YY (3-36); D011333:Pro-Opiomelanocortin; D052216:Glucagon-Like Peptide 1; D018021:Lithium Chloride