1. PYY3-36 injection in mice produces an acute anorexigenic effect followed by a delayed orexigenic effect not observed with other anorexigenic gut hormones.
- Author
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Parkinson JR, Dhillo WS, Small CJ, Chaudhri OB, Bewick GA, Pritchard I, Moore S, Ghatei MA, and Bloom SR
- Subjects
- Agouti-Related Protein genetics, Agouti-Related Protein metabolism, Animals, Antimanic Agents pharmacology, Dose-Response Relationship, Drug, Fasting, Glucagon-Like Peptide 1 pharmacology, Hypothalamus drug effects, Hypothalamus physiology, Incretins pharmacology, Injections, Intraperitoneal, Lithium Chloride pharmacology, Male, Mice, Mice, Inbred C57BL, Neuropeptide Y genetics, Neuropeptide Y metabolism, Orexins, Oxyntomodulin pharmacology, Peptide Fragments, Pro-Opiomelanocortin genetics, Pro-Opiomelanocortin metabolism, RNA, Messenger metabolism, Specific Pathogen-Free Organisms, Appetite Depressants pharmacology, Eating drug effects, Intracellular Signaling Peptides and Proteins metabolism, Neuropeptides metabolism, Peptide YY pharmacology, Satiety Response drug effects
- Abstract
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.
- Published
- 2008
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