The lipid messenger OEA links dietary fat intake to satiety

Cell Metab. 2008 Oct;8(4):281-288. doi: 10.1016/j.cmet.2008.08.005.


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-alpha (PPAR-alpha). 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-alpha 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD36 Antigens / metabolism
  • Dietary Fats*
  • Eating / drug effects*
  • Endocannabinoids
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Feeding Behavior / drug effects*
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / metabolism
  • Intestine, Small / anatomy & histology
  • Lipid Metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Oleic Acid / metabolism
  • Oleic Acids / pharmacology*
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Satiation / physiology*
  • Signal Transduction / physiology


  • CD36 Antigens
  • Dietary Fats
  • Endocannabinoids
  • Oleic Acids
  • PPAR alpha
  • oleoylethanolamide
  • Oleic Acid