Lipid Profiling Reveals Tissue‐Specific Differences for Ethanolamide Lipids in Mice Lacking Fatty Acid Amide Hydrolase

Kilaru, Aruna; Isaac, Giorgis; Tamura, Pamela; Baxter, David W.; Duncan, Scott R.; Venables, Barney J.; Welti, Ruth; Koulen, Peter; Chapman, Kent D.

doi:10.1007/s11745-010-3457-5

Cited by 34 publications

(29 citation statements)

References 41 publications

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“…A total lipid extract from 100 mg brain, which is an extremely lipid‐rich tissue, would have to be diluted in a volume of 10 mL or more for routine lipidomic analysis. While other analytical methods applied to NAPE skip extensive sample preparation methods 6, 7, 30, 32, 34, the presented sample cleanup by SPE eliminates many highly abundant lipid classes such as triacylglycerols that consequently enables reconstitution of the NAPE‐containing fraction in a much smaller volume (200 μL). Preliminary testing during method development showed no analyte losses caused by SPE sample preparation.…”

Section: Resultsmentioning

confidence: 99%

Quantitative analysis of N‐acylphosphatidylethanolamine molecular species in rat brain using solid‐phase extraction combined with reversed‐phase chromatography and tandem mass spectrometry

Triebl

Weissengruber

Trötzmüller

et al. 2016

J of Separation Science

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A novel method for the sensitive and selective identification and quantification of N‐acylphosphatidylethanolamine molecular species was developed. Samples were prepared using a combination of liquid–liquid and solid‐phase extraction, and intact N‐acylphosphatidylethanolamine species were determined by reversed‐phase high‐performance liquid chromatography coupled to positive electrospray tandem mass spectrometry. As a result of their biological functions as precursors for N‐acylethanolamines and as signaling molecules, tissue concentrations of N‐acylphosphatidylethanolamines are very low, and their analysis is additionally hindered by the vast excess of other sample components. Our sample preparation methods are able to selectively separate the analytes of interest from any expected biological interferences. Finally, the highest selectivity is achieved by coupling chromatographic separation and two N‐acyl chain specific selected reaction monitoring scans per analyte, enabling identification of both the N‐acyl chain and the phosphatidylethanolamine moiety. The validated method is suitable for the reliable quantification of N‐acylphosphatidylethanolamine species from rat brain with a lower limit of quantification of 10 pmol/g and a linear range up to 2300 pmol/g. In total, 41 N‐acylphosphatidylethanolamine molecular species with six different N‐acyl chains, amounting to a total concentration of 3 nmol/g, were quantified.

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Section: Resultsmentioning

confidence: 99%

Quantitative analysis of N‐acylphosphatidylethanolamine molecular species in rat brain using solid‐phase extraction combined with reversed‐phase chromatography and tandem mass spectrometry

Triebl

Weissengruber

Trötzmüller

et al. 2016

J of Separation Science

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“…Several previous studies have reported changes in NAE and NAT lipids in rodents with pharmacological or genetic disruptions of FAAH ( 6,12,17,18,24,25 ). Most of these reports focus on a single or select number of tissues, and few, if any, have compared acute versus chronic disruption of FAAH in a quantitative manner.…”

Section: Discussionmentioning

confidence: 99%

An anatomical and temporal portrait of physiological substrates for fatty acid amide hydrolase

Long

LaCava

Jin

et al. 2011

Journal of Lipid Research

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tors that also respond to ⌬ 9 -tetrahydrocannabinol (THC), the psychoactive component of marijuana ( 7 ). The genetic or pharmacological inactivation of FAAH results in substantial increases in brain concentrations of anandamide and other N -acyl ethanolamine (NAE) lipids and produces several CB1-dependent neurobehavioral effects in rodents, including anxiolysis ( 8, 9 ), anti-depression ( 10 ), and anti-nociception ( 6,11,12 ). Interestingly, these effects are not accompanied by the cognitive and motor dysfunctions associated with direct CB1 agonists such as THC. Taken together, these fi ndings indicate that FAAH is a key regulator of endocannabinoid activity in vivo and suggest further that the enzyme might represent a therapeutic target for the treatment of pain and other nervous system disorders ( 13,14 ).FAAH-disrupted mice have also shown some phenotypes that are not reversed by the administration of CB1 or CB2 antagonists ( 12,15,16 ), suggesting that anandamide and/ or other FAAH substrates possess bioactivities that extend beyond the endocannabinoid system. To more broadly explore the physiological substrate pool regulated by FAAH, our laboratory has analyzed FAAH( Ϫ / Ϫ ) mice using a metabolomics method based on untargeted LC-MS ( 17 ). This approach confi rmed known elevations in anandamide and other NAEs in brains and livers of FAAH( Ϫ / Ϫ ) mice and also uncovered a novel class of natural products regulated by FAAH, the N -acyl taurines (NATs). Subsequent in vitro studies showed that FAAH can hydrolyze NATs and that NATs are agonists of the transient receptor potential family of ion channels at concentrations approximately equal to or lower than those found in certain tissues from FAAH( Ϫ / Ϫ ) mice ( 17, 18 ). Fatty acid amide hydrolase (FAAH) is an integral membrane serine hydrolase that degrades a number of bioactive lipid amides, including the endocannabinoid anandamide ( N -arachidonoyl ethanolamine) ( 1, 2 ). Anandamide acts as an endogenous ligand for the CB1 and CB2 receptors ( 3-6 ), which are two G-protein-coupled recep- Abstract Fatty acid amide hydrolase (FAAH) regulates amidated lipid transmitters, including the endocannabinoid anandamide and its N -acyl ethanolamine (NAE) congeners and transient receptor potential channel agonists N -acyl taurines (NATs). Using both the FAAH inhibitor PF-3845 and FAAH( ؊ /؊

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“…Levels of NAE 16:0 and 18:1 were higher in the DBA/2 heart when compared to other mouse strains,31,32 however, lower levels of NAE 20:4 were measured. Brain levels of all NAEs were lower in the DBA/2 mice when compared to other mouse strains and species 31,33. Very low basal levels of NAE 18:2 have been reported in the brain at ~2 pmol/g FW34 and were not detected in this study.…”

Section: Discussionmentioning

confidence: 60%

N-Palmitoylethanolamine depot injection increased its tissue levels and those of other acylethanolamide lipids

Grillo

Keereetaweep

Grillo

et al. 2013

DDDT

Self Cite

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N-Palmitoylethanolamine (NAE 16:0) is an endogenous lipid signaling molecule that has limited water solubility, and its action is short-lived due to its rapid metabolism. This poses a problem for use in vivo as oral administration requires a high concentration for significant levels to reach target tissues, and injection of the compound in a dimethyl sulfoxide- or ethanol-based vehicle is usually not desirable during long-term treatment. A depot injection of NAE 16:0 was successfully emulsified in sterile corn oil (10 mg/kg) and administered in young DBA/2 mice in order to elevate baseline levels of NAE 16:0 in target tissues. NAE 16:0 levels were increased in various tissues, particularly in the retina, 24 and 48 hours following injections. Increases ranged between 22% and 215% (above basal levels) in blood serum, heart, brain, and retina and induced an entourage effect by increasing levels of other 18 carbon N-Acylethanolamines (NAEs), which ranged between 31% and 117% above baseline. These results indicate that NAE 16:0 can be used as a depot preparation, avoiding the use of inadequate vehicles, and can provide the basis for designing tissue-specific dosing regimens for therapies involving NAEs and related compounds.

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Lipid Profiling Reveals Tissue‐Specific Differences for Ethanolamide Lipids in Mice Lacking Fatty Acid Amide Hydrolase

Cited by 34 publications

References 41 publications

Quantitative analysis of N‐acylphosphatidylethanolamine molecular species in rat brain using solid‐phase extraction combined with reversed‐phase chromatography and tandem mass spectrometry

Quantitative analysis of N‐acylphosphatidylethanolamine molecular species in rat brain using solid‐phase extraction combined with reversed‐phase chromatography and tandem mass spectrometry

An anatomical and temporal portrait of physiological substrates for fatty acid amide hydrolase

N-Palmitoylethanolamine depot injection increased its tissue levels and those of other acylethanolamide lipids

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