The lipid messenger OEA links dietary fat intake to satiety.
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.
Diabetes Research Center, Departments of Medicine and Neuroscience, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY.
Gary J
GJ
Schwartz
Department of Pharmacology, University of California, Irvine, California.
Jin
J
Fu
Department of Pharmacology, University of California, Irvine, California.
Giuseppe
G
Astarita
Diabetes Research Center, Departments of Medicine and Neuroscience, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY.
Xiaosong
X
Li
Department of Human Physiology and Pharmacology, University of Rome 'La Sapienza', Rome, Italy.
Silvana
S
Gaetani
Department of Human Physiology and Pharmacology, University of Rome 'La Sapienza', Rome, Italy.
Patrizia
P
Campolongo
Department of Human Physiology and Pharmacology, University of Rome 'La Sapienza', Rome, Italy.
Vincenzo
V
Cuomo
Department of Pharmacology, University of California, Irvine, California.|Unit of Drug Discovery and Development, Italian Institute of Technology, Genoa, Italy.
Daniele
D
Piomelli
D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D004041:Dietary Fats; D004435:Eating / Q000187:drug effects*; D063388:Endocannabinoids; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism; D007421:Intestine, Small / Q000033:anatomy & histology; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019301:Oleic Acid / Q000378:metabolism; D009829:Oleic Acids / Q000494:pharmacology*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012527:Satiation / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D018955:CD36 Antigens; D004041:Dietary Fats; D063388:Endocannabinoids; D009829:Oleic Acids; D047493:PPAR alpha; C488250:oleoylethanolamide; D019301:Oleic Acid