A Gut Lipid Messenger Links Excess Dietary Fat to Dopamine Deficiency

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Science  16 Aug 2013:
Vol. 341, Issue 6147, pp. 800-802
DOI: 10.1126/science.1239275

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Food as Reward

Why does ice cream taste so good? High-fat foods activate a reward circuit in the brain involving dopamine, a neurotransmitter that regulates pleasure. Overconsumption of high-fat foods is thought to dampen this dopamine-induced reward sensation, leading to compensatory consumption of even more high-fat foods. The mechanisms by which dietary fat in the gut “talks” to the dopamine reward circuit are unclear. Tellez et al. (p. 800) suggest that an intestinal lipid messenger called oleoylethanolamine (OEA) may play a role—at least in mice. Mice on a high-fat diet had unusually low levels of intestinal OEA and exhibited deficient dopaminergic responses to gut stimulation with high-fat lipids. Infusion of OEA into these mice restored the dopaminergic response, and mice that had been accustomed to a high-fat diet began to eat more low-fat foods.


Excessive intake of dietary fats leads to diminished brain dopaminergic function. It has been proposed that dopamine deficiency exacerbates obesity by provoking compensatory overfeeding as one way to restore reward sensitivity. However, the physiological mechanisms linking prolonged high-fat intake to dopamine deficiency remain elusive. We show that administering oleoylethanolamine, a gastrointestinal lipid messenger whose synthesis is suppressed after prolonged high-fat exposure, is sufficient to restore gut-stimulated dopamine release in high-fat–fed mice. Administering oleoylethanolamine to high-fat–fed mice also eliminated motivation deficits during flavorless intragastric feeding and increased oral intake of low-fat emulsions. Our findings suggest that high-fat–induced gastrointestinal dysfunctions play a key role in dopamine deficiency and that restoring gut-generated lipid signaling may increase the reward value of less palatable, yet healthier, foods.

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