Neuropharmacology postdoc Nick DiPatrizio was stumped. His advisor, University of California, Irvine, researcher Daniele Piomelli, had discovered eight years earlier that hungry rats have high levels of endocannabinoids, endogenous molecules that bind to the same receptors as the active ingredient in marijuana.
Now, in 2009, DiPatrizio was trying to identify exactly where and how those molecules were controlling food intake in rats. But under specific feeding conditions, he couldn’t locate any changes in endocannabinoid levels in the brain, which is flush with endocannabinoid receptors and the obvious place to look for behavioral signals.
Piomelli gently chastised his mentee. “He said, ‘You’re being neurocentric. Remember, there’s a body attached to the head. Look in the other organs of the body,’ ” recalls DiPatrizio. So the young scientist persisted, and eventually discovered that hunger—and the taste of fat—leads to increased endocannabinoid levels in the jejunum, a part of the small intestine. Endocannabinoid signaling in the gut, not the brain, was controlling food intake in the rodents in response to tasting fats.1
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