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NAPE-PLD in the ventral tegmental area regulates reward events, feeding and energy homeostasis

The N-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) catalyzes the production of N-acylethanolamines (NAEs), a family of endogenous bioactive lipids, which are involved in various biological processes ranging from neuronal functions to energy homeostasis and feeding behaviors. Rew...

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Detalles Bibliográficos
Autores principales: Castel, Julien, Li, Guangping, Oriane, Onimus, Leishman, Emma, Cani, Patrice D., Bradshaw, Heather, Mackie, Ken, Everard, Amandine, Luquet, Serge, Gangarossa, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543029/
https://www.ncbi.nlm.nih.gov/pubmed/37790425
http://dx.doi.org/10.21203/rs.3.rs-3199777/v1
Descripción
Sumario:The N-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) catalyzes the production of N-acylethanolamines (NAEs), a family of endogenous bioactive lipids, which are involved in various biological processes ranging from neuronal functions to energy homeostasis and feeding behaviors. Reward-dependent behaviors depend on dopamine (DA) transmission between the ventral tegmental area (VTA) and the nucleus accumbens (NAc), which conveys reward-values and scales reinforced behaviors. However, whether and how NAPE-PLD may contribute to the regulation of feeding and reward-dependent behaviors has not yet been investigated. This biological question is of paramount importance since NAEs are altered in obesity and metabolic disorders. Here, we show that transcriptomic meta-analysis highlights a potential role for NAPE-PLD within the VTA(®)NAc circuit. Using brain-specific invalidation approaches, we report that the integrity of NAPE-PLD is required for the proper homeostasis of NAEs within the midbrain VTA and it affects food-reward behaviors. Moreover, region-specific knock-down of NAPE-PLD in the VTA enhanced food-reward seeking and reinforced behaviors, which were associated with increased in vivo DA release dynamics in response to both food and non-food-related rewards together with heightened tropism towards food consumption. Furthermore, midbrain knock-down of NAPE-PLD, which increased energy expenditure and adapted nutrient partitioning, elicited a relative protection against high-fat diet-mediated body fat gain and obesity-associated metabolic features. In conclusion, these findings reveal a new key role of VTA NAPE-PLD in shaping DA-dependent events, feeding behaviors and energy homeostasis, thus providing new insights on the regulation of body metabolism.