Lipid Profiling Reveals Tissue-Specific Differences for Ethanolamide Lipids in Mice Lacking Fatty Acid Amide Hydrolase
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N-Acylethanolamines (NAE) are fatty acid derivatives, some of which function as endocannabinoids in mammals. NAE metabolism involves common (phosphatidylethanolamines, PEs) and uncommon (N-acylphosphatidylethanolamines, NAPEs) membrane phospholipids. Here we have identified and quantified more than a hundred metabolites in the NAE/endocannabinoid pathway in mouse brain and heart tissues, including many previously unreported molecular species of NAPE. We found that brain tissue of mice lacking fatty acid amide hydrolase (FAAH−/−) had elevated PE and NAPE molecular species in addition to elevated NAEs, suggesting that FAAH activity participates in the overall regulation of this pathway. This perturbation of the NAE pathway in brain was not observed in heart tissue of FAAH−/− mice, indicating that metabolic regulation of the NAE pathway differs in these two organs and the metabolic enzymes that catabolize NAEs are most likely differentially distributed and/or regulated. Targeted lipidomics analysis, like that presented here, will continue to provide important insights into cellular lipid signaling networks.
KeywordsFAAH Endocannabinoids N-Acylethanolamines Lipid profiling Lipid signaling Lipid mediators Mass spectrometry
Fatty acid amide hydrolase
Free fatty acid
Designates carbon chain length: total number of carbon–carbon double bonds
We would like to thank Mary R. Roth for expert technical assistance. This work was supported by a seed grant from the University of North Texas and by a grant from the US Department of Energy, Office of Basic Energy Sciences (DE-FG02-05ER15647). This study was supported in part by NIH grants MD001633 from NCMHD (R.S.D.), EY014227, AG010485, AG022550, and AG027956 (P.K.) as well as by The Garvey Texas Foundation and the Felix and Carmen Sabates Missouri Endowed Chair in Vision Research (P.K.). Instrument acquisition and method development at the Kansas Lipidomics Research Center were supported by NSF grants MCB 0455318 and DBI 0521587, K-INBRE (NIH Grant P20 RR16475 from the INBRE program of the National Center for Research Resources), and NSF EPSCoR grant EPS-0236913 with matching support from the State of Kansas through Kansas Technology Enterprise Corporation and Kansas State University.
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