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

Cell Metabolism
Chloé BerlandSerge H Luquet

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.

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Citations

Jun 9, 2020·The Journal of Clinical Investigation·Yuki Yasumoto, Tamas L Horvath
Aug 6, 2020·International Journal of Molecular Sciences·Marie-Cécile Alexandre-GouabauVincent Paillé
Nov 1, 2020·International Journal of Molecular Sciences·Marie A LabouesseTommaso Patriarchi
Jun 22, 2021·Trends in Endocrinology and Metabolism : TEM·Chloé BerlandGiuseppe Gangarossa
Jun 15, 2021·Frontiers in Endocrinology·Andrew FolickMartin Valdearcos
Aug 13, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Laura L KoekkoekSusanne E la Fleur
Nov 6, 2021·Journal of Neuroendocrinology·Vincent Prevot

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