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

作者：Long Jonathan Z; LaCava Melanie; Jin Xin; Cravatt Benjamin F^*

来源：The Journal of Lipid Research, 2011, 52(2): 337-344.

DOI：10.1194/jlr.M012153

• anandamide
• endocannabinoid
• metabolomics
• taurine

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(-/-) mice, we present a global analysis of changes in NAE and NAT metabolism caused by FAAH disruption in central and peripheral tissues. Elevations in anandamide (and other NAEs) were tissue dependent, with the most dramatic changes occurring in brain, testis, and liver of PF-3845-treated or FAAH(-/-) mice. Polyunsaturated NATs accumulated to very high amounts in the liver, kidney, and plasma of these animals. The NAT profile in brain tissue was markedly different and punctuated by significant increases in long-chain NATs found exclusively in FAAH(-/-), but not in PF-3845-treated animals. Suspecting that this difference might reflect a slow pathway for NAT biosynthesis, we treated mice chronically with PF-3845 for 6 days and observed robust elevations in brain NATs. These studies, taken together, define the anatomical and temporal features of FAAH-mediated NAE and NAT metabolism, which are complemented and probably influenced by kinetically distinguishable biosynthetic pathways that produce these lipids in vivo.-Long, J. Z., M. LaCava, X. Jin, and B. F. Cravatt. An anatomical and temporal portrait of physiological substrates for fatty acid amide hydrolase. J. Lipid Res. 2011. 52: 337-344.

• 出版日期2011-2