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Mol Psychiatry. 2014 Oct;19(10):1095-105. doi: 10.1038/mp.2014.31. Epub 2014 Apr 15.

Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding.

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Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, Paris, France.
Institut Jacques Monod, Sorbonne Paris Cité, Université Paris Diderot, Paris, France.
Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health, München/Neuherberg, Germany.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Department of Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands.
1] Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health, München/Neuherberg, Germany [2] Division of Metabolic Diseases, Department of Medicine, Technische Universität München, München, Germany.
Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Department of Neurosciences, University of California, La Jolla, CA, USA.


Circulating triglycerides (TGs) normally increase after a meal but are altered in pathophysiological conditions, such as obesity. Although TG metabolism in the brain remains poorly understood, several brain structures express enzymes that process TG-enriched particles, including mesolimbic structures. For this reason, and because consumption of high-fat diet alters dopamine signaling, we tested the hypothesis that TG might directly target mesolimbic reward circuits to control reward-seeking behaviors. We found that the delivery of small amounts of TG to the brain through the carotid artery rapidly reduced both spontaneous and amphetamine-induced locomotion, abolished preference for palatable food and reduced the motivation to engage in food-seeking behavior. Conversely, targeted disruption of the TG-hydrolyzing enzyme lipoprotein lipase specifically in the nucleus accumbens increased palatable food preference and food-seeking behavior. Finally, prolonged TG perfusion resulted in a return to normal palatable food preference despite continued locomotor suppression, suggesting that adaptive mechanisms occur. These findings reveal new mechanisms by which dietary fat may alter mesolimbic circuit function and reward seeking.

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