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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/E698    most recent 00405.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Parkinson, J. R. C. Articles by Bloom, S. R. PubMed PubMed Citation Articles by Parkinson, J. R. C. Articles by Bloom, S. R.

PYY_3-36 injection in mice produces an acute anorexigenic effect followed by a delayed orexigenic effect not observed with other anorexigenic gut hormones

Department of Metabolic Medicine, Hammersmith Hospital, Imperial College London, London, United Kingdom

Submitted 26 June 2007 ; accepted in final form 11 February 2008

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 Ile³ 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.

peptide YY_3-36; appetite; gut hormones