University Paris Diderot, Sorbonne Paris Cité - Unité de Biologie Fonctionnelle et Adaptative, CNRS UMR 8251; German Research Center for Environmental Health, Helmholtz Center Munich, Helmholtz Diabetes Center
University of Bordeaux - Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, UMR5287; University of Bordeaux - Centre National de la Recherche Scientifique (CNRS)
Novo Nordisk - Global Research; Technical University of Denmark, Department of Applied Mathematics and Computer Science, Image Analysis & Computer Graphics; Gubra ApS
University of Paris 6 Pierre et Marie Curie, Equipe Neurophysiologie et Comportement (NPC), Neuroscience Paris-Seine – IBPS – UPMC UM CR18 – CNRS UMR 8246 – INSERM U1130
University of Paris 6 Pierre et Marie Curie, Equipe Neurophysiologie et Comportement (NPC), Neuroscience Paris-Seine – IBPS – UPMC UM CR18 – CNRS UMR 8246 – INSERM U113
Novo Nordisk - Global Research; Technical University of Denmark, Department of Applied Mathematics and Computer Science, Image Analysis & Computer Graphics; Gubra ApS
University of Bordeaux - Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, UMR5287; University of Bordeaux, Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, UMR5287, Centre National de la Recherche Scientifique (CNRS)
German Research Center for Environmental Health, Helmholtz Center Munich, Helmholtz Diabetes Center; Technische Universität München (TUM) - Division of Metabolic Diseases; Technische Universität München (TUM) - Institute for Advanced Study
University of Paris 6 Pierre et Marie Curie, Equipe Neurophysiologie et Comportement (NPC), Neuroscience Paris-Seine – IBPS – UPMC UM CR18 – CNRS UMR 8246 – INSERM U1130
University Paris Diderot, Sorbonne Paris Cité - Unité de Biologie Fonctionnelle et Adaptative, CNRS UMR 8251; Modern Diet and Physiology Research Center
Emerging evidence suggests that energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system and can promote the development of compulsive-like feeding, reward dysfunction, and ultimately weight gain. Yet the mechanisms by which metabolic signals influence MCL circuitry to control behavior remain poorly understood. Circulating triglycerides (TG) are a conserved post-prandial metabolic signature among mammals and high plasma TG are associated with reduced reward responsiveness in humans. Here, we show that the TG-processing enzyme lipoprotein lipase (LPL) is enriched throughout the MCL of both mouse and human, including DA-releasing neurons in the ventral tegmental area and DA-receptive neurons in the striatum. Using brain-specific TG delivery in mice, we show that nutritional TG are metabolized within the MCL system where they acutely control D2 DA receptor (DRD2) signaling. We also show that TG are directly reinforcing in mice, and that central TG sensing relies on LPL activity in the MCL. Likewise, in humans, post-prandial TG excursions modulate brain response to food cues in MCL with the direction of the association determined by a DRD2 dependent genotype. Collectively, these findings reveal a mechanism by which dietary TG directly alter MCL signaling to regulate behavior, providing a new mechanistic basis by which energy-rich diets can lead to adaptations in DA signaling that underlie compulsive behavior.
Berland, Chloé and Gangarossa, Giuseppe and Nakamura, Yuko and Sullivan, Mary and Davis, Xue and Shenasa, Mohammad Ali and Caille, Stephanie and Jensen, Casper Bo and Castel, Julien and Morel, Chloé and Martin, Claire and Tolu, Stefania and Marti, Fabio and Hecksher-Sørensen, Jacob and Cador, Martine and Tschöp, Matthias H. and Faure, Philippe and Hnasko, Thomas S. and Small, Dana M. and Luquet, Serge, The Dopamine Receptor Subtype 2 (DRD2) Regulates the Central Reinforcing Actions of Dietary Lipids in Humans and Rodents (May 3, 2019). Available at SSRN: https://ssrn.com/abstract=3382218 or http://dx.doi.org/10.2139/ssrn.3382218
This version of the paper has not been formally peer reviewed.
University of Paris 6 Pierre et Marie Curie, Equipe Neurophysiologie et Comportement (NPC), Neuroscience Paris-Seine – IBPS – UPMC UM CR18 – CNRS UMR 8246 – INSERM U1130
University of Paris 6 Pierre et Marie Curie, Equipe Neurophysiologie et Comportement (NPC), Neuroscience Paris-Seine – IBPS – UPMC UM CR18 – CNRS UMR 8246 – INSERM U113
University of Paris 6 Pierre et Marie Curie, Equipe Neurophysiologie et Comportement (NPC), Neuroscience Paris-Seine – IBPS – UPMC UM CR18 – CNRS UMR 8246 – INSERM U1130
Subscribe to this free journal for more curated articles on this topic
FOLLOWERS
20
PAPERS
9,210
Feedback
Feedback to SSRN
If you need immediate assistance, call 877-SSRNHelp (877 777 6435) in the United States, or +1 212 448 2500 outside of the United States, 8:30AM to 6:00PM U.S. Eastern, Monday - Friday.