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Publication : Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons.

First Author  Berland C Year  2020
Journal  Cell Metab Volume  31
Issue  4 Pages  773-790.e11
PubMed ID  32142669 Mgi Jnum  J:287740
Mgi Id  MGI:6406611 Doi  10.1016/j.cmet.2020.02.010
Citation  Berland C, et al. (2020) Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons. Cell Metab 31(4):773-790.e11
abstractText  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.
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