Biosynthetic Pathways of Bioactive N-Acylethanolamines in Brain

Tsuboi, Kazuhito; Ikematsu, Natsuki; Uyama, Toru; Deutsch, Dale G.; Tokumura, Akira; Ueda, Natsuo

doi:10.2174/1871527311312010005

Cited by 51 publications

(35 citation statements)

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“…OEA and PEA are chemically related to anandamide and, in neurons, they are produced by the activity of the same PLD that catalyzes anandamide release 82 (Figure 4). Nevertheless, the mechanisms governing the formation of these FAEs differ from those involved in the production of anandamide in two important aspects.…”

Section: Endogenous Ppar-α Agonists: Homeostatic Control Of Nociceptionmentioning

confidence: 99%

Peripheral gating of pain signals by endogenous lipid mediators

2014

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Primary sensory afferents and their neighboring host-defense cells are a rich source of lipid-derived mediators that contribute to the sensation of pain caused by tissue damage and inflammation. But an increasing number of lipid molecules have been shown to act in an opposite way, to suppress the inflammatory process, restore homeostasis in damaged tissues and attenuate pain sensitivity by regulating neural pathways that transmit nociceptive signals from the periphery of the body to the central nervous system.

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Section: Endogenous Ppar-α Agonists: Homeostatic Control Of Nociceptionmentioning

confidence: 99%

Peripheral gating of pain signals by endogenous lipid mediators

2014

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“…Further, the O3PUFA-derived NAEs identified in this study are precursors of docosahexaenoyl ethanolamine (DHEA; synaptamide) and eicosapentaenoyl ethanolamine (EPEA), which bind to cannabinoid receptors in rats (Sheskin et al, 1997) and may contribute to the beneficial effects mediated by dietary O3PFAs (Balvers et al, 2010; Meijerink et al, 2011; Shinohara et al, 2012). Although the metabolic pathways involved in NAE biosynthesis remain unclear, our results strongly suggest that NAPE-PLD-independent (N-acyl phosphatidyl ethanolamine phospholipase D) pathways are activated in chronic SCI and represent a promising therapeutic target (Tsuboi et al, 2013). Because NAEs can modify the response to nociceptive stimuli and are tightly regulated by diet, O3PUFAs could have important implications for chronic pain management.…”

Section: Discussionmentioning

confidence: 88%

Metabolomics uncovers dietary omega-3 fatty acid-derived metabolites implicated in anti-nociceptive responses after experimental spinal cord injury

et al. 2013

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Chronic neuropathic pain is a frequent comorbidity following spinal cord injury (SCI) and often fails to respond to conventional pain management strategies. Preventive administration of docosahexaenoic acid (DHA) or consumption of a diet rich in omega-3 polyunsaturated fatty acids (O3PUFAs) confers potent prophylaxis against SCI and improves functional recovery. The present study examines whether this novel dietary strategy provides significant antinociceptive benefits in rats experiencing SCI-induced pain. Rats were fed control chow or chow enriched with O3PUFAs for 8 weeks before being subjected to sham or cord contusion surgeries, continuing the same diets after surgery for another 8 more weeks. The paw sensitivity to noxious heat was quantified for at least 8 weeks post-SCI using the Hargreaves test. We found that SCI rats consuming the preventive O3PUFA-enriched diet exhibited a significant reduction in thermal hyperalgesia compared to those consuming the normal diet. Functional neurometabolomic profiling revealed a distinctive deregulation in the metabolism of endocannabinoids (eCB) and related N-acyl ethanolamines (NAEs) at 8 weeks post-SCI. We found that O3PUFAs consumption led to a robust accumulation of novel NAE precursors, including the glycerophospho-containing docosahexaenoyl ethanolamine (DHEA), docosapentaenoyl ethanolamine (DPEA), and eicosapentaenoyl ethanolamine (EPEA). The tissue levels of these metabolites were significantly correlated with the antihyperalgesic phenotype. In addition, rats consuming the O3PUFA-rich diet showed reduced sprouting of nociceptive fibers containing CGRP and dorsal horn neuron p38 MAPK expression, well-established biomarkers of pain. The spinal cord levels of inositols were positively correlated with thermal hyperalgesia, supporting their role as biomarkers of chronic neuropathic pain. Notably, the O3PUFA-rich dietary intervention reduced the levels of these metabolites. Collectively, these results demonstrate the prophylactic value of dietary O3PUFA against SCI-mediated chronic pain.

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“…Thus far, NAPE-PLD and glycerophosphodiesterase 1 (GDE1) have been shown to be involved in OEA biosynthesis [42, 43]. Previous studies demonstrated that feeding-dependent mobilization of jejunal OEA is associated with alterations in NAPE-PLD activity and expression in chow-fed rats [29].…”

Section: Discussionmentioning

confidence: 99%

Feeding-induced oleoylethanolamide mobilization is disrupted in the gut of diet-induced obese rodents

Igarashi

DiPatrizio

Narayanaswami

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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The gastrointestinal tract plays a critical role in the regulation of energy homeostasis by initiating neural and hormonal responses to the ingestion of nutrients. In addition to peptide hormones, such as cholecystokinin (CKK) and peptide YY (PYY), the lipid-derived mediator oleoylethanolamide (OEA) has been implicated in the control of satiety. Previous studies in humans and rodent models have shown that obesity is associated with changes in CCK, PYY and other gut-derived peptide hormones, which may contribute to decreased satiety and increased energy intake. In the present study, we show that small-intestinal OEA production is disrupted in the gut of diet-induced obese (DIO) rats and mice. In lean rodents, feeding or duodenal infusion of Intralipid® or pure oleic acid stimulate jejunal OEA mobilization. This response is strikingly absent in DIO rats and mice. Confirming previous reports, we found that feeding rats or mice a high-fat diet for 7 days is sufficient to suppress jejunal OEA mobilization. Surprisingly, a similar effect is elicited by feeding rats and mice a high-sucrose low-fat diet for 7 days. Collectively, our findings suggest that high fat-induced obesity is accompanied by alterations in the post-digestive machinery responsible for OEA biosynthesis, which may contribute to reduced satiety and hyperphagia.

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Biosynthetic Pathways of Bioactive N-Acylethanolamines in Brain

Cited by 51 publications

References 0 publications

Peripheral gating of pain signals by endogenous lipid mediators

Peripheral gating of pain signals by endogenous lipid mediators

Metabolomics uncovers dietary omega-3 fatty acid-derived metabolites implicated in anti-nociceptive responses after experimental spinal cord injury

Feeding-induced oleoylethanolamide mobilization is disrupted in the gut of diet-induced obese rodents

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