Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons
- 4 March 2020
- journal article
- research article
- Published by Elsevier BV in Cell Metabolism
- Vol. 31 (4), 773-790.e11
- https://doi.org/10.1016/j.cmet.2020.02.010
Abstract
Energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system and can promote reward dysfunctions, compulsive feeding, and weight gain. Yet the mechanisms by which nutrients influence the MCL circuitry remain elusive. Here, we show that nutritional triglycerides (TGs), a conserved post-prandial metabolic signature among mammals, can be metabolized within the MCL system and modulate DA-associated behaviors by gating the activity of dopamine receptor subtype 2 (DRD2)-expressing neurons through a mechanism that involves the action of the lipoprotein lipase (LPL). Further, we show that in humans, post-prandial TG excursions modulate brain responses to food cues in individuals carrying a genetic risk for reduced DRD2 signaling. Collectively, these findings unveil a novel mechanism by which dietary TGs directly alter signaling in the reward circuit to regulate behavior, thereby providing a new mechanistic basis by which energy-rich diets may lead to (mal)adaptations in DA signaling that underlie reward deficit and compulsive behavior.Keywords
Funding Information
- Agence Nationale de la Recherche
This publication has 82 references indexed in Scilit:
- GABAergic signaling by AgRP neurons prevents anorexia via a melanocortin-independent mechanismEuropean Journal of Pharmacology, 2011
- Deficiency of Lipoprotein Lipase in Neurons Modifies the Regulation of Energy Balance and Leads to ObesityCell Metabolism, 2011
- Circulating triglycerides after a high-fat meal: Predictor of increased caloric intake, orexigenic peptide expression, and dietary obesityBrain Research, 2009
- ‘Liking’ and ‘wanting’ food rewards: Brain substrates and roles in eating disordersPhysiology & Behavior, 2009
- D2 dopamine receptor Taq1A polymorphism, body weight, and dietary intake in type 2 diabetesNutrition, 2009
- Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat.Behavioral Neuroscience, 2008
- Relation of reward from food intake and anticipated food intake to obesity: A functional magnetic resonance imaging study.Journal of Abnormal Psychology, 2008
- Application of a Translational Profiling Approach for the Comparative Analysis of CNS Cell TypesCell, 2008
- Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factorsNeuroImage, 2008
- Food reinforcement, the dopamine D₂ receptor genotype, and energy intake in obese and nonobese humans.Behavioral Neuroscience, 2007