title: Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding.
abstract: 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.
authors.affiliation: Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Cansell
authors.affiliation: Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Castel
authors.affiliation: Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, Paris, France.
authors.forename: R G P
authors.initials: RG
authors.lastname: Denis
authors.affiliation: Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Rouch
authors.affiliation: Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, Paris, France.
authors.forename: A-S
authors.initials: AS
authors.lastname: Delbes
authors.affiliation: Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Martinez
authors.affiliation: Institut Jacques Monod, Sorbonne Paris Cité, Université Paris Diderot, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Mestivier
authors.affiliation: Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health, München/Neuherberg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Finan
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Maldonado-Aviles
authors.affiliation: Department of Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Rijnsburger
authors.affiliation: 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.
authors.forename: M H
authors.initials: MH
authors.lastname: Tschöp
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: DiLeone
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Eckel
authors.affiliation: Department of Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: S E
authors.initials: SE
authors.lastname: la Fleur
authors.affiliation: Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Magnan
authors.affiliation: Department of Neurosciences, University of California, La Jolla, CA, USA.
authors.forename: T S
authors.initials: TS
authors.lastname: Hnasko
authors.affiliation: Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Luquet
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002339:Carotid Arteries / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D005247:Feeding Behavior / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009042:Motivation / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D012201:Reward; D014280:Triglycerides / Q000097:blood*
chemical_list: D000697:Central Nervous System Stimulants; D014280:Triglycerides; D000661:Amphetamine; D008071:Lipoprotein Lipase
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