Napepld, or N-acyl phosphatidylethanolamine phospholipase D, is an enzyme of the endocannabinoid system. It catalyzes the production of N-acylethanolamines (NAEs), a family of endogenous bioactive lipids involved in various biological processes, from neuronal functions to energy homeostasis and feeding behaviors [1,2,3].

In a murine model with an inducible Napepld deletion in intestinal epithelial cells (NapepldΔIEC), the mice displayed lower hypothalamic levels of N-oleoylethanolamine (OEA) in response to high-fat-diet (HFD), along with lower mRNA expression of anorexigenic Pomc in the hypothalamus after lipid challenge, suggesting an impairment of the gut-brain axis in regulating appetite [2]. In another study, region-specific knock-down of Napepld in the ventral tegmental area (VTA) enhanced food-reward seeking and reinforced behaviors, increased in vivo DA release in response to rewards, and protected against high-fat diet-mediated body fat gain and obesity-associated metabolic features [3].

In conclusion, Napepld plays a crucial role in regulating appetite via the gut-brain axis and in controlling reward-related behaviors and energy homeostasis. Mouse models with Napepld deletion or knockdown have revealed its significance in obesity-related metabolic conditions, providing insights into potential therapeutic targets for obesity and associated metabolic disorders [2,3].

References:

1. Minor, K M, Letko, A, Becker, D, Mickelson, J R, Drögemüller, C. 2018. Canine NAPEPLD-associated models of human myelin disorders. In Scientific reports, 8, 5818. doi:10.1038/s41598-018-23938-7. https://pubmed.ncbi.nlm.nih.gov/29643404/

2. Rastelli, Marialetizia, Van Hul, Matthias, Terrasi, Romano, Muccioli, Giulio G, Cani, Patrice D. 2020. Intestinal NAPE-PLD contributes to short-term regulation of food intake via gut-to-brain axis. In American journal of physiology. Endocrinology and metabolism, 319, E647-E657. doi:10.1152/ajpendo.00146.2020. https://pubmed.ncbi.nlm.nih.gov/32776827/

3. Castel, Julien, Li, Guangping, Onimus, Oriane, Luquet, Serge, Gangarossa, Giuseppe. 2024. NAPE-PLD in the ventral tegmental area regulates reward events, feeding and energy homeostasis. In Molecular psychiatry, 29, 1478-1490. doi:10.1038/s41380-024-02427-6. https://pubmed.ncbi.nlm.nih.gov/38361126/