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Fatty acid binding proteins are novel modulators of synaptic epoxyeicosatrienoic acid signaling in the brain.

ABSTRACT: Fatty acid binding proteins (FABPs) govern intracellular lipid transport to cytosolic organelles and nuclear receptors. More recently, FABP5 has emerged as a key regulator of synaptic endocannabinoid signaling, suggesting that FABPs may broadly regulate the signaling of neuroactive lipids in the brain. Herein, we demonstrate that brain-expressed FABPs (FABP3, FABP5, and FABP7) interact with epoxyeicosatrienoic acids (EETs) and the peroxisome proliferator-activated receptor gamma agonist 15-deoxy-Δ^12,14-Prostaglandin J2 (15d-PGJ₂). Among these lipids, EETs displayed highest affinities for FABP3 and FABP5, and 11,12-EET was identified as the preferred FABP ligand. Similarly, 15d-PGJ₂ interacted with FABP3 and FABP5 while binding to FABP7 was markedly lower. Molecular modeling revealed unique binding interactions of the ligands within the FABP binding pockets and highlighted major contributions of van der Waals clashes and acyl chain solvent exposure in dictating FABP affinity and specificity. Functional studies demonstrated that endogenous EETs gate the strength of CA1 hippocampal glutamate synapses and that this function was impaired following FABP inhibition. As such, the present study reveals that FABPs control EET-mediated synaptic gating, thereby expanding the functional roles of this protein family in regulating neuronal lipid signaling.

SUBMITTER: Glaser ST

PROVIDER: S-EPMC10502087 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Fatty acid binding proteins are novel modulators of synaptic epoxyeicosatrienoic acid signaling in the brain.

Glaser Sherrye T ST Jayanetti Kalani K Oubraim Saida S Hillowe Andrew A Frank Elena E Jong Jason J Wang Liqun L Wang Hehe H Ojima Iwao I Haj-Dahmane Samir S Kaczocha Martin M

Scientific reports 20230914 1

Fatty acid binding proteins (FABPs) govern intracellular lipid transport to cytosolic organelles and nuclear receptors. More recently, FABP5 has emerged as a key regulator of synaptic endocannabinoid signaling, suggesting that FABPs may broadly regulate the signaling of neuroactive lipids in the brain. Herein, we demonstrate that brain-expressed FABPs (FABP3, FABP5, and FABP7) interact with epoxyeicosatrienoic acids (EETs) and the peroxisome proliferator-activated receptor gamma agonist 15-deoxy ...[more]

PMID: 37709856

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Fatty acid binding proteins are novel modulators of synaptic epoxyeicosatrienoic acid signaling in the brain.

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Fatty acid binding proteins are novel modulators of synaptic epoxyeicosatrienoic acid signaling in the brain.

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