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FABP ‐1 gene ablation impacts brain endocannabinoid system in male mice
Author(s) -
Martin Gregory G.,
Chung Sarah,
Landrock Danilo,
Landrock Kerstin K.,
Huang Huan,
Dangott Lawrence J.,
Peng Xiaoxue,
Kaczocha Martin,
Seeger Drew R.,
Murphy Eric J.,
Golovko Mikhail Y.,
Kier Ann B.,
Schroeder Friedhelm
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13664
Subject(s) - endocannabinoid system , fatty acid binding protein , biology , arachidonic acid , cytosol , medicine , anandamide , cannabinoid receptor , endocrinology , fatty acid , central nervous system , biochemistry , receptor , pharmacology , enzyme , gene , agonist
Liver fatty acid‐binding protein ( FABP 1, L‐ FABP ) has high affinity for and enhances uptake of arachidonic acid ( ARA , C20:4, n‐6) which, when esterified to phospholipids, is the requisite precursor for synthesis of endocannabinoids ( EC ) such as arachidonoylethanolamide ( AEA ) and 2‐arachidonoylglycerol (2‐ AG ). The brain derives most of its ARA from plasma, taking up ARA and transporting it intracellularly via cytosolic fatty acid‐binding proteins ( FABP s 3,5, and 7) localized within the brain. In contrast, the much more prevalent cytosolic FABP 1 is not detectable in the brain but is instead highly expressed in the liver. Therefore, the possibility that FABP 1 outside the central nervous system may regulate brain AEA and 2‐ AG was examined in wild‐type ( WT ) and FABP 1 null ( LKO ) male mice. LKO increased brain levels of AA ‐containing EC ( AEA , 2‐ AG ), correlating with increased free and total ARA in brain and serum. LKO also increased brain levels of non‐ ARA that contain potentiating endocannabinoids ( EC *) such as oleoyl ethanolamide ( OEA ), PEA , 2‐ OG , and 2‐ PG . Concomitantly, LKO decreased serum total ARA ‐containing EC , but not non‐ ARA endocannabinoids. LKO did not elicit these changes in the brain EC and EC * as a result of compensatory up‐regulation of brain protein levels of enzymes in EC synthesis ( NAPEPLD , DAGL α) or cytosolic EC chaperone proteins ( FABP s 3, 5, 7, SCP ‐2, HSP 70), or cannabinoid receptors ( CB 1, TRVP 1). These data show for the first time that the non‐ CNS fatty acid‐binding protein FABP 1 markedly affected brain levels of both ARA ‐containing endocannabinoids ( AEA , 2‐ AG ) as well as their non‐ ARA potentiating endocannabinoids.Fatty acid‐binding protein‐1 (FABP‐1) is not detectable in brain but instead is highly expressed in liver. The possibility that FABP1 outside the central nervous system may regulate brain endocannabinoids arachidonoylethanolamide (AEA) and 2‐arachidonoylglycerol (2‐AG) was examined in wild‐type (WT) and FABP‐1 null (LKO) male mice. LKO increased brain levels of arachidonic acid‐containing endocannabinoids (AEA, 2‐AG), correlating with increased free and total arachidonic acid in brain and serum. Read the Editorial Highlight for this article on page 371 .