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更新于：2025-01-23

NAPE-PLD

更新于：2025-01-23

基本信息

别名

C7orf18、chromosome 7 open reading frame 18, N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D、FMP30

+ [5]

简介

D-type phospholipase that hydrolyzes N-acyl-phosphatidylethanolamines (NAPEs) to produce bioactive N-acylethanolamines/fatty acid ethanolamides (NAEs/FAEs) and phosphatidic acid (PubMed:14634025, PubMed:16527816, PubMed:27571266, PubMed:25684574). Cleaves the terminal phosphodiester bond of diacyl- and alkenylacyl-NAPEs, primarily playing a role in the generation of long-chain saturated and monounsaturated NAEs in the brain (By similarity). May control NAPE homeostasis in dopaminergic neuron membranes and regulate neuron survival, partly through RAC1 activation (By similarity). As a regulator of lipid metabolism in the adipose tissue, mediates the crosstalk between adipocytes, gut microbiota and immune cells to control body temperature and weight. In particular, regulates energy homeostasis by promoting cold-induced brown or beige adipocyte differentiation program to generate heat from fatty acids and glucose. Has limited D-type phospholipase activity toward N-acyl lyso-NAPEs (By similarity).

关联

项与 NAPE-PLD 相关的药物

LEI-401

靶点

NAPE-PLD

作用机制

NAPE-PLD 抑制剂

在研机构

University of Leiden

原研机构

University of Leiden

在研适应症

神经母细胞瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 NAPE-PLD 相关的临床结果

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100 项与 NAPE-PLD 相关的转化医学

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0 项与 NAPE-PLD 相关的专利（医药）

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284

项与 NAPE-PLD 相关的文献（医药）

2025-02-01·Neuroscience

Escitalopram reverses anxiety-like and despair behavior and affects endocannabinoid-related genes expression in the brain of adolescent male rats subjected to early life stress

Article

作者: Gołyszny, Miłosz ; Zieliński, Michał ; Starowicz, Katarzyna ; Popiołek-Barczyk, Katarzyna ; Dragon, Jonasz ; Obuchowicz, Ewa

Due to the increasing prevalence of depressive and anxiety disorders in youth, a growing interest in the endocannabinoid system (ECS) as a potential alternative target point for treatment arised. This study aimed to investigate whether chronic administration of escitalopram reverses behavioral changes induced by maternal separation in male adolescent Wistar rats and explore the corresponding neurochemical changes in the ECS. The pups were separated from their dams for 360 min daily from postnatal day (PND) 2 until PND 15. Later, male rats were administered escitalopram (10 mg/kg i.p.) during their adolescent period (PND 35 - PND 55). Behavioral assessments were conducted in late adolescence (PND 54 - PND 57) in one group, and brain structures were dissected for biochemical analysis in the subsequent group of rats on PND 56. Expression of genes encoding: CB1 receptor, enzyme that catalyzes synthesis (NAPE-PLD) and degradation (FAAH) of anandamide (a full agonist of CB1 receptor) was evaluated using qRT-PCR. The corresponding protein levels were estimated via Western blot analysis. Our study revealed that maternal separation induced anxiety and despair-like behavior in adolescent rats. Escitalopram reversed anxiety-like behavior and attenuated signs of despair behavior. The escitalopram administration has been followed by a decrease in the studied genes expression in the amygdala, the hypothalamus, and the hippocampus, what might suggest that the endocannabinoid system is involved in the mechanism of its action in adolescents. However Western blot analysis did not indicate significant alterations in the protein levels, so more detailed studies are needed to verify this hypothesis.

2024-06-01·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Endocannabinoid remodeling in murine cachexic muscle associates with catabolic and metabolic regulation

Article

作者: Hiroux, Charlotte ; Dalle, Sebastiaan ; Koppo, Katrien

Muscle degeneration is a common feature in cancer cachexia that cannot be reversed. Recent advances show that the endocannabinoid system, and more particularly cannabinoid receptor 1 (CB1), regulates muscle processes, including metabolism, anabolism and regenerative capacity. However, it is unclear whether muscle endocannabinoids, their receptors and enzymes are responsive to cachexia and exercise. Therefore, this study investigated whether cachexia and exercise affected muscle endocannabinoid signaling, and whether CB1 expression correlated with markers of muscle anabolism, catabolism and metabolism. Male BALB/c mice were injected with PBS (CON) or C26 colon carcinoma cells (C26) and had access to wheel running (VWR) or remained sedentary (n = 5-6/group). Mice were sacrificed 18 days upon PBS/tumor cell injection. Cachexic mice exhibited a lower muscle CB1 expression (-43 %; p < 0.001) and lower levels of the endocannabinoid anandamide (AEA; -22 %; p = 0.044), as well as a lower expression of the AEA-synthesizing enzyme NAPE-PLD (-37 %; p < 0.001), whereas the expression of the AEA degrading enzyme FAAH was higher (+160 %; p < 0.001). The 2-AG-degrading enzyme MAGL, was lower in cachexic muscle (-34 %; p = 0.007), but 2-AG and its synthetizing enzyme DAGLβ were not different between CON and C26. VWR increased muscle CB1 (+25 %; p = 0.005) and increased MAGL expression (+30 %; p = 0.035). CB1 expression correlated with muscle mass, markers of metabolism (e.g. p-AMPK, PGC1α) and of catabolism (e.g. p-FOXO, LC3b, Atg5). Our findings depict an emerging role of the endocannabinoid system in muscle physiology. Future studies should elaborate how this translates into potential therapies to combat cancer cachexia, and other degenerative conditions.

2024-05-01·Molecular Psychiatry

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

Article

作者: Castel, Julien ; Leishman, Emma ; Bradshaw, Heather ; Gangarossa, Giuseppe ; Everard, Amandine ; Onimus, Oriane ; Cani, Patrice D ; Luquet, Serge ; Li, Guangping ; Mackie, Ken

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.

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