Science 16 August 2013:
Vol. 341 no. 6147 pp. 800-802
- Luis A. Tellez1,2,
- Sara Medina1,
- Wenfei Han1,2,3,
- Jozelia G. Ferreira1,2,
- Paula Licona-Limón4,
- Xueying Ren1,2,
- TuKiet T. Lam5,
- Gary J. Schwartz6,
- Ivan E. de Araujo1,2,*
+ Author Affiliations
1The John B. Pierce Laboratory, New Haven, CT 06519, USA.
2Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA.
3School of Stomatology, Tongji University, Shanghai 200072, China.
4Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
5W. M. Keck Foundation Biotechnology Resource Laboratory, Yale University, New Haven, CT 06511, USA.
6Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA.
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.