Summary: Dietary triglycerides directly alter signaling in the reward circuit to regulate behavior. The findings reveal a potential mechanism by which triglyceride-rich diets may lead to adaptions in dopamine signaling that underlie reward deficit and compulsive behaviors.
Source: CNRS
Energy-dense food, obesity and compulsive food intake bordering addiction: the scientific literature has been pointing to connections between these for years. Scientists at the CNRS and Université de Paris have just shown for the first time how fatty nutrients act on the brain in the reward circuit. Published in Cell Metabolism on 5 March 2020, these results shed new light on the connection between food and eating disorders.
This recent work, directed by scientists at the Unité de biologie fonctionnelle et adaptative (CNRS/Université de Paris), show that triglycerides, the nutrients that constitute animal fats, vegetable oils and dairy products, interact with certain neurons in the reward circuit and reduce their excitability in mice, both in vitro and in vivo. These neurons carry a specific type of dopamine-receptor, and their activity strengthens reward-seeking behaviour. The scientists also observed that the manipulation of triglyceride levels in the brain of mice changes many behaviours associated with dopamine, like pleasure and motivation to collect food.
The study is completed by observations of brain activity in humans in response to a food odour compared with their blood triglyceride level after a meal. The research team has shown that activity in the prefrontal cortex, one of the regions of the reward circuit that makes connections between a food’s odour, its taste and the pleasure that it causes, is directly correlated with the quantity of triglycerides circulating in the blood. The higher it is, the lower the prefrontal cortex’s response to a food odour. This suggests that the activity of important brain structures in the reward system can be directly modified by a lipid nutrient.
Usually, triglycerides only circulate in the blood after a meal. The exception is obese patients, for whom doctors often observe abnormally high triglyceride levels all day long. In this context, this study offers a new framework for potentially explaining why ever-wider access to rich foods may contribute to the establishment of compulsive dietary problems and increase obesity rates.
Source:
CNRS
Media Contacts:
Francois Maginiot – CNRS
Image Source:
The image is credited to Chloe Berland et al.
Original Research: Closed access
“Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons”. Chloe Berland et al.
Cell Metabolism doi:10.1016/j.cmet.2020.02.010.
Abstract
Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons
Highlights
• Dopamine receptor type 2 (DRD2)-expressing neurons respond to dietary triglycerides (TGs)
• Dietary TGs modulate dopamine-dependent behaviors
• Lipoprotein lipase participates in the action of TGs on the reward circuit
• In humans, plasma TGs influence brain responses to food
Summary
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.
