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

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 dif...

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Bibliographic Details
Published in:Lipids 2016-09, Vol.51 (9), p.1007-1020
Main Authors: Martin, Gregory G., Chung, Sarah, Landrock, Danilo, Landrock, Kerstin K., Dangott, Lawrence J., Peng, Xiaoxue, Kaczocha, Martin, Murphy, Eric J., Kier, Ann B., Schroeder, Friedhelm
Format: Article
Language:English
Subjects:
Animals
Arachidonic Acid - metabolism
Biomedical and Life Sciences
Brain
Brain - metabolism
Endocannabinoid
Endocannabinoids - metabolism
Ethanolamines - metabolism
FABP1
Fatty Acid-Binding Proteins - deficiency
Fatty acids
Female
Gene ablation
Glycerides - metabolism
Life Sciences
Lipidology
Male
Medical Biochemistry
Medicinal Chemistry
Mice
Microbial Genetics and Genomics
Mouse
Neurochemistry
Nutrition
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Summary: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).
ISSN:0024-4201
1558-9307
DOI:10.1007/s11745-016-4175-4