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Female Mice are Resistant to Fabp1 Gene Ablation-Induced Alterations in Brain Endocannabinoid Levels

  • Original Article
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Lipids

Abstract

Although liver fatty acid binding protein (FABP1, L-FABP) is not detectable in the brain, Fabp1 gene ablation (LKO) markedly increases endocannabinoids (EC) in brains of male mice. Since the brain EC system of females differs significantly from that of males, it was important to determine if LKO differently impacted the brain EC system. LKO did not alter brain levels of arachidonic acid (ARA)-containing EC, i.e. arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), but decreased non-ARA-containing N-acylethanolamides (OEA, PEA) and 2-oleoylglycerol (2-OG) that potentiate the actions of AEA and 2-AG. These changes in brain potentiating EC levels were not associated with: (1) a net decrease in levels of brain membrane proteins associated with fatty acid uptake and EC synthesis; (2) a net increase in brain protein levels of cytosolic EC chaperones and enzymes in EC degradation; or (3) increased brain protein levels of EC receptors (CB1, TRVP1). Instead, the reduced or opposite responsiveness of female brain EC levels to loss of FABP1 (LKO) correlated with intrinsically lower FABP1 level in livers of WT females than males. These data show that female mouse brain endocannabinoid levels were unchanged (AEA, 2-AG) or decreased (OEA, PEA, 2-OG) by complete loss of FABP1 (LKO).

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Abbreviations

ACBP:

Acyl-CoA binding protein

ARA:

Arachidonic acid

AEA, anandamide:

Arachidonoylethanolamide

2-AG:

2-Arachidonoylglycerol

CB1, Cnr1 :

Cannabinoid receptor-1

CB2, Cnr2 :

Cannabinoid receptor-2

DAGL-α, Dagla :

Diacylglycerol lipase α

DHEA:

Docosahexaenoylethanolamide

EPEA:

Eicosapentaenoylethanolamide

EC:

Endocannabinoid

FAAH, Faah :

Fatty acid amide hydrolase

FABP1, L-FABP:

Liver fatty acid binding protein-1

FABP-3, Fabp3 :

Fatty acid binding protein-3

FABP-5, Fabp5 :

Fatty acid binding protein-5

FABP-7, Fabp7 :

Fatty acid binding protein-7

FAT/CD36:

Fatty acid translocase/thrombospondin receptor

FATP-1:

Fatty acid transport protein-1

FATP-4:

Fatty acid transport protein-4

LKO:

Fabp1 gene ablated mouse on C57BL/6NCr background

GPCR:

G protein coupled receptor

GRK-2, Adrbk2 :

G protein coupled receptor kinase-2

LCFA:

Long chain fatty acid

LCFA-CoA:

Long chain fatty acyl-CoA

2-MG:

2-Monoacylglycerol

MGL, Mgll :

2-Monoacylglycerol lipase

NAAA, Naaa :

N-Acylethanolamide-hydrolyzing acid amidase

NAE:

N-Acylethanolamide

NAPE:

N-Acylphosphatidylethanolamide

NAPE-PLD, Nape-pld :

N-Acylphosphatidylethanolamide phospholipase-D

OEA:

Oleoylethanolamide

2-OG:

2-Oleoylglycerol

PEA:

Palmitoylethanolamide

2-PG:

2-Palmitoyl glycerol

SCP-2, Scp2 :

Sterol carrier protein-2

TRVP-1, vanilloid receptor-1, Trvp-1 :

Transient receptor potential cation channel subfamily V member 1

WT:

Wild-type C57BL/6NCr mouse

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Acknowledgments

The work presented herein was supported in part by the US Public Health Service/National Institutes of Health Grant R25 OD016574 (S.C., A.B.K.), Merial Veterinary Scholars Program, CVM (S.C., A.B.K.), and DA035949 (M.K.). The authors acknowledge ThermoFisher Scientific for use of the Exactive Orbitrap mass spectrometer.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Texas A&M University, 4466 TAMU, College Station, TX, 77843-4466, USA

    Gregory G. Martin, Kerstin K. Landrock & Friedhelm Schroeder

  2. Department of Pathobiology, Texas A&M University, College Station, TX, 77843-4466, USA

    Sarah Chung, Danilo Landrock & Ann B. Kier

  3. Protein Chemistry Laboratory, Texas A&M University, College Station, TX, 77843-2128, USA

    Lawrence J. Dangott

  4. Department of Anesthesiology, Stony Brook University, Stony Brook, NY, 11794, USA

    Xiaoxue Peng & Martin Kaczocha

  5. Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, 58202-9037, USA

    Eric J. Murphy

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  1. Gregory G. Martin
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Correspondence to Friedhelm Schroeder.

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Martin, G.G., Chung, S., Landrock, D. et al. Female Mice are Resistant to Fabp1 Gene Ablation-Induced Alterations in Brain Endocannabinoid Levels. Lipids 51, 1007–1020 (2016). https://doi.org/10.1007/s11745-016-4175-4

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