Endocannabinoid signal in the gut controls dietary fat intake

Nicholas V. DiPatrizio, Giuseppe Astarita, Gary Schwartz, Xiaosong Li, Daniele Piomelli

Research output: Contribution to journalArticlepeer-review

143 Scopus citations


Oral sensory signals drive dietary fat intake, but the neural mechanisms underlying this process are largely unknown. The endocannabinoid system has gained recent attention for its central and peripheral roles in regulating food intake, energy balance, and reward. Here, we used a sham-feeding paradigm, which isolates orosensory from postingestive influences of foods, to examine whether endocannabinoid signaling participates in the positive feedback control of fat intake. Sham feeding a lipid-based meal stimulated endocannabinoid mobilization in the rat proximal small intestine by altering enzymatic activities that control endocannabinoid metabolism. This effect was abolished by surgical transection of the vagus nerve and was not observed in other peripheral organs or in brain regions that control feeding. Sham feeding of a nutritionally complete liquid meal produced a similar response to that of fat, whereas protein or carbohydrate alone had no such effect. Local infusion of the CB 1-cannabinoid receptor antagonist, rimonabant, into the duodenummarkedly reduced fat sham feeding. Similarly to rimonabant, systemic administration of the peripherally restricted CB 1-receptor antagonist, URB 447, attenuated sham feeding of lipid. Collectively, the results suggest that the endocannabinoid system in the gut exerts a powerful regulatory control over fat intake and might be a target for antiobesity drugs.

Original languageEnglish (US)
Pages (from-to)12904-12908
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number31
StatePublished - Aug 2 2011

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Endocannabinoid signal in the gut controls dietary fat intake'. Together they form a unique fingerprint.

Cite this