Publ. Version/Full Text online available 04/2021 () as soon as is submitted to ZB.
Circulating triglycerides gate dopamine-associated behaviors through DRD2-expressing neurons.
Cell Metab. 31, 773-790 (2020)
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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, postprandial 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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Publication type Article: Journal article
Document type Scientific Article
Keywords Dopamine ; Dopamine Receptor D2 ; Fmri ; Food-reward ; Lipoprotein Lipase ; Nucleus Accumbens ; Striatum ; Triglycerides ; Ventral Tegmental Area; High-fat Diet; Lipoprotein-lipase; Nucleus-accumbens; Receptor Gene; D2 Receptors; Energy-balance; Weight-gain; Food-intake; Long-term; Brain
Institute(s) Institute of Diabetes and Obesity (IDO)