title: FABP-1 gene ablation impacts brain endocannabinoid system in male mice.
abstract: Liver fatty acid-binding protein (FABP1, 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 (FABPs 3,5, and 7) localized within the brain. In contrast, the much more prevalent cytosolic FABP1 is not detectable in the brain but is instead highly expressed in the liver. Therefore, the possibility that FABP1 outside the central nervous system may regulate brain AEA and 2-AG was examined in wild-type (WT) and FABP1 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, DAGLα) or cytosolic EC chaperone proteins (FABPs 3, 5, 7, SCP-2, HSP70), or cannabinoid receptors (CB1, TRVP1). These data show for the first time that the non-CNS fatty acid-binding protein FABP1 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.
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, College Station, Texas, USA.
authors.forename: Gregory G
authors.identifier: 0000-0002-0092-4612
authors.initials: GG
authors.lastname: Martin
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, College Station, Texas, USA.|Department of Pathobiology, Texas A&M University, College Station, Texas, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Chung
authors.affiliation: Department of Pathobiology, Texas A&M University, College Station, Texas, USA.
authors.forename: Danilo
authors.initials: D
authors.lastname: Landrock
authors.affiliation: Department of Pathobiology, Texas A&M University, College Station, Texas, USA.
authors.forename: Kerstin K
authors.initials: KK
authors.lastname: Landrock
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, College Station, Texas, USA.
authors.forename: Huan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, USA.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Dangott
authors.affiliation: Department of Anesthesiology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Anesthesiology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Kaczocha
authors.affiliation: Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota, USA.
authors.forename: Drew R
authors.initials: DR
authors.lastname: Seeger
authors.affiliation: Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Murphy
authors.affiliation: Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota, USA.
authors.forename: Mikhail Y
authors.initials: MY
authors.lastname: Golovko
authors.affiliation: Department of Pathobiology, Texas A&M University, College Station, Texas, USA.
authors.forename: Ann B
authors.initials: AB
authors.lastname: Kier
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, College Station, Texas, USA.
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Schroeder
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D063388:Endocannabinoids / Q000235:genetics / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics*; D005989:Glycerides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009829:Oleic Acids / Q000378:metabolism*; D053284:Polyunsaturated Alkamides / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; C493320:Fabp1 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005989:Glycerides; D009829:Oleic Acids; D053284:Polyunsaturated Alkamides; C488250:oleoylethanolamide; C078814:anandamide
keywords: brain; endocannabinoid; gene ablation; liver fatty acid-binding protein; mouse