The Lipid Messenger OEA Links Dietary Fat Intake to Satiety

Gary J. Schwartz, Jin Fu, Giuseppe Astarita, Xiaosong Li, Silvana Gaetani, Patrizia Campolongo, Vincenzo Cuomo, Daniele Piomelli

Research output: Contribution to journalArticlepeer-review

303 Scopus citations


The association between fat consumption and obesity underscores the need to identify physiological signals that control fat intake. Previous studies have shown that feeding stimulates small-intestinal mucosal cells to produce the lipid messenger oleoylethanolamide (OEA) which, when administered as a drug, decreases meal frequency by engaging peroxisome proliferator-activated receptors-α (PPAR-α). Here, we report that duodenal infusion of fat stimulates OEA mobilization in the proximal small intestine, whereas infusion of protein or carbohydrate does not. OEA production utilizes dietary oleic acid as a substrate and is disrupted in mutant mice lacking the membrane fatty-acid transporter CD36. Targeted disruption of CD36 or PPAR-α abrogates the satiety response induced by fat. The results suggest that activation of small-intestinal OEA mobilization, enabled by CD36-mediated uptake of dietary oleic acid, serves as a molecular sensor linking fat ingestion to satiety.

Original languageEnglish (US)
Pages (from-to)281-288
Number of pages8
JournalCell metabolism
Issue number4
StatePublished - Oct 8 2008



ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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