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fabp1a

Official Full Name
fatty acid binding protein 1a, liver
Organism
Danio rerio
GeneID
791610
Background
Predicted to enable fatty acid binding activity. Predicted to be involved in fatty acid transport. Predicted to be located in cytoplasm. Predicted to be active in cytosol and nucleus. Is expressed in hepatocyte; intestine; and liver. Orthologous to human FABP1 (fatty acid binding protein 1). [provided by Alliance of Genome Resources, Feb 2025]
Synonyms
fabp1; L-FABP;

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Detailed Information

FABP1 is a novel binding protein for hepatic endocannabinoid and cannabinoid, which are lipophilic molecules that work on intercellular targets with the help of cytosolic proteins. Even though how the three common fatty acid binding proteins (FABP3, -5, -7) work in brain is clear, there is little known about the functionality of such hydrophobic endocannabinoid and cannabinoid in liver. High affinity with arachidonic acid (ARA) and ARA-CoA of the most pronounced hepatic fatty acid binding protein FABP1 or L-FABP suggests its might affinity with ARA derived endocannabinoid (AEA and 2-AG). In fact, more than high affinity with ECs shows in displacement of FABP-1-bound fluorescent ligands and its intrinsic fluorescence quenching, it also exerts same degree affinity with non-ARA-containing EC, FABP1 inhibitor, EC reuptake/hydrolysis inhibitor and Phyto cannabinoids, while relatively less for synthetic cannabinoid receptor (CBR) agonist and antagonists.

Zebrafish gene, fabp1a, which corresponds to gene coding for human protein FABP1, was firstly cloned and sequenced by Mukesh K. Sharma. Zebrafish fabp1a assigned to linkage 5, which shows conserved syntenies to segment of FABP1 locus harbored mouse chromosome 6, rat chromosome 4 and human chromosome 2. The occurrence of zebrafish fabp1a becoming as mammalian FABP1 orthologs is estimated to be in the whole-genome duplication event 200-450 million years ago by the phylogenetic analysis. Revelation of its unique and differential pattern of expression by in situ hybridization to whole-mount embryos of fabp1a suggests that there may be a hierarchical sub functionalization accounted for the retention of duplicated gene in the zebrafish genome following their duplication from the vertebrate genome.

The amino acid sequences for zebrafish FABP1a encoded by fabp1a genes do not cluster as closely as other sister duplicate genes from this zebrafish multigene family, such as FABP7a and FABP7b, or CRABP1a and CRABP1b. One explanation for this phenomenon may be reduced selective pressure on one of the duplicated genes.

FABP1 inhibition works as a novel machinery in regulating autophagy-lysosomal for hepatic steatosis prevention

Exercise works as the main preventive strategy and first-line therapy for nonalcoholic fatty liver disease (NAFLD), one of most prevalent diseases worldwide. However, its hidden mechanism has not been fully clarified till now. The test of high-fat diet feeding accompanied with 12-week duration swimming exercise on C57BL/6 mice showed exercise accounting for alleviation of hepatic lipid accumulation and hepatocyte damage. Tandem mass tag-based quantitative proteomic analyses revealed that swimming downregulated FABP1 signaling pathway is closely related with lipid metabolism. And swimming exerted protection over NAFLD can be offset by overexpression of FABP1, more detailed, recovery of lysosomal function, resorted to lysosomal proteolysis and lysosomal acidification maintenance, through exercise, can significantly enhance autophagic clearance and subsequently alleviate hepatic steatosis.

Prevention of exercise exerted on HFD-induced hepatic steatosis by FABP1 pathway inhibitionFig 1. Prevention of exercise exerted on HFD-induced hepatic steatosis by FABP1 pathway inhibition (Feng Gao et al. 2019)

References:

  1. Kaczocha, M., Vivieca, S., Sun, J. (2012) 'Fatty acid binding proteins transport N-acylethanolamines to nuclear receptors and are targets of endocannabinoid transport inhibitors', Journal of Biological chemistry, doi: 10.1074/jbc.M111.304907.
  2. Huan Huang, Avery L. McIntosh, Gregory G. Martin. (2016) 'FABP1: A Novel Hepatic Endocannabinoid and Cannabinoid Binding Protein', Biochemistry, doi: 10.1021/acs.biochem.6b00446.
  3. Huifeng Pi,Mengyu Liu,Yu Xi. (2019) 'Long-term exercise prevents hepatic steatosis: a novel role of FABP1 in regulation of autophagy-lysosomal machinery', The FASEB Journal, doi: 10.1096/fj.201900812R.
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