論文

査読有り
2014年8月

Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Gustavo Provensi
  • Roberto Coccurello
  • Hayato Umehara
  • Leonardo Munari
  • Giacomo Giacovazzo
  • Nicoletta Galeotti
  • Daniele Nosi
  • Silvana Gaetani
  • Adele Romano
  • Anna Moles
  • Patrizio Blandina
  • Maria Beatrice Passani
  • 全て表示

111
31
開始ページ
11527
終了ページ
11532
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.1322016111
出版者・発行元
NATL ACAD SCIENCES

Key factors driving eating behavior are hunger and satiety, which are controlled by a complex interplay of central neurotransmitter systems and peripheral stimuli. The lipid-derived messenger oleoylethanolamide (OEA) is released by enterocytes in response to fat intake and indirectly signals satiety to hypothalamic nuclei. Brain histamine is released during the appetitive phase to provide a high level of arousal in anticipation of feeding, and mediates satiety. However, despite the possible functional overlap of satiety signals, it is not knownwhether histamine participates in OEA-induced hypophagia. Using different experimental settings and diets, we report that the anorexiant effect of OEA is significantly attenuated in mice deficient in the histamine-synthesizing enzyme histidine decarboxylase (HDC-KO) or acutely depleted of histamine via interocerebroventricular infusion of the HDC blocker alpha-fluoromethylhistidine (alpha-FMH). alpha-FMH abolished OEA-induced early occurrence of satiety onset while increasing histamine release in the CNS with an H-3 receptor antagonist-increased hypophagia. OEA augmented histamine release in the cortex of fasted mice within a time window compatible to its anorexic effects. OEA also increased c-Fos expression in the oxytocin neurons of the paraventricular nuclei of WT but not HDC-KO mice. The density of c-Fos immunoreactive neurons in other brain regions that receive histaminergic innervation and participate in the expression of feeding behavior was comparable in OEA-treated WT and HDC-KO mice. Our results demonstrate that OEA requires the integrity of the brain histamine system to fully exert its hypophagic effect and that the oxytocin neuron-rich nuclei are the likely hypothalamic area where brain histamine influences the central effects of OEA.

リンク情報
DOI
https://doi.org/10.1073/pnas.1322016111
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25049422
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000339807200062&DestApp=WOS_CPL
ID情報
  • DOI : 10.1073/pnas.1322016111
  • ISSN : 0027-8424
  • PubMed ID : 25049422
  • Web of Science ID : WOS:000339807200062

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