Alternative titles; symbols
HGNC Approved Gene Symbol: FABP1
Cytogenetic location: 2p11.2 Genomic coordinates (GRCh38): 2:88,122,982-88,128,062 (from NCBI)
FABP1, or liver fatty acid-binding protein, is an abundant constituent of cytoplasm that regulates lipid transport and metabolism. It binds free fatty acids, their CoA derivatives, bilirubin, organic anions, and other small molecules. See also FABP2 (134640), FABP3 (134651), and FABP4 (600434). FABP1 is required for cholesterol synthesis and metabolism (summary by Chen et al., 1986).
Chen et al. (1986) stated that human FABP1 contains 127 amino acids and has a calculated molecular mass of 14.2 kD. Amino acids 12 to 30 of FABP1 contain lipid-binding sites.
Using cDNA of FABP1 in Southern analysis of human/mouse cell hybrid DNA, Chen et al. (1986) assigned the FABP1 gene to chromosome 2p. Sparkes et al. (1987) confirmed the assignment to chromosome 2 and regionalized the gene to 2p11 by in situ hybridization.
Sweetser et al. (1987) found that the mouse Fabp1 gene maps to chromosome 6, within 3 cM of the lymphocyte antigen-2 (Ly2) locus. They suggested that Fabp1 may be identical to major liver protein-1 (Lvp1), which is encoded by a gene situated within 1 cM of Ly2.
Using recombinant mouse protein, Huang et al. (2016) showed that Fabp1 bound arachidonic acid (ARA)-derived endocannabinoids (ECs) with high affinity. Fabp1 also bound most non-ARA-containing ECs, Fabp1 inhibitors, EC uptake/hydrolysis inhibitors, and phytocannabinoids with high affinity. It bound synthetic cannabinoid receptor (CBR) agonists and antagonists with lower affinity. Human SCP2 (184755) also bound ECs directly, as well as inhibitors of SCP2 and FABPs, suggesting that it functions as an additional cytosolic EC chaperone.
Using purified recombinant proteins, Storey et al. (2017) showed that neither human SCP2 nor mouse Fabp1 bound phytol, but that both had high affinity for its metabolite, phytanic acid.
Rodriguez Sawicki et al. (2017) found that FABP1 knockdown decreased uptake rate and total cellular incorporation of oleic acid in Caco2 cells. FABP1-deficient Caco2 cells showed altered composition of basolaterally secreted lipids and reduced cell proliferation. In addition, oleic acid incorporation and distribution into lipid classes were reduced in undifferentiated FABP1-knockout Caco2 cells.
Huang et al. (2016) found that livers of male Fabp1 -/- mice, but not female Fabp1 -/- mice, had increased EC levels. Increased EC levels in male Fabp1 -/- mice correlated with complete loss of Fabp1, decreased level of Scp2, and decreased levels of degradative enzymes. The authors concluded that FABP1 is not only the most prominent EC- and cannabinoid-binding protein, but that it also impacts hepatic EC levels.
Storey et al. (2017) found that loss of both Fabp1 and Scp2 in mice exacerbated hepatic accumulation of phytol metabolites in females and less so in males. At the same time, dietary phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female wildtype and mutant mice. Moreover, in both wildtype and mutant female mice, dietary phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs while decreasing the peroxidizability index. However, in male mice, dietary phytol selectively increased the saturated/unsaturated ratio only in mutant mice, while decreasing the peroxidizability index in both wildtype and mutant mice. The results suggested a greater role for Fabp1 in transporting phytanic acid from the endoplasmic reticulum to peroxisomes, and for Scp2 in intraperoxisomal transport of phytanoyl-CoA and/or subsequent metabolites to oxidative enzymes within the peroxisomal matrix.
Mukai et al. (2017) found that knockdown of Fabp1 decreased liver weight and hepatic triglyceride content in mice, because knockdown attenuated synthesis of hepatic fatty acid and triglyceride. In addition, Fabp1 knockdown attenuated both inflammation and oxidative stress in mouse liver. The authors proposed that FABP1 reduction in liver may be an effective treatment for nonalcoholic fatty liver disease (see 613282).
Xu et al. (2019) found that Lfabp -/- mice become more obese than wildtype mice when fed a high-fat diet, but that they were protected from high-fat feeding-induced exercise decline. High-fat diet-fed Lfabp -/- mice had increased muscle substrate availability and greater muscle mitochondrial function, but their muscle fiber composition was not altered. Lfabp -/- mice showed efficient substrate utilization in muscles during exercise. In line with the muscle metabolic changes, PCR analysis revealed differential metabolic regulation and basal metabolites in Lfabp -/- muscle compared with wildtype.
Chen, S. H., Van Tuinen, P., Ledbetter, D. H., Smith, L. C., Chan, L. Human liver fatty acid binding protein gene is located on chromosome 2. Somat. Cell Molec. Genet. 12: 303-306, 1986. [PubMed: 3012800] [Full Text: https://doi.org/10.1007/BF01570790]
Huang, H., McIntosh, A. L., Martin, G. G., Landrock, D., Chung, S., Landrock, K. K., Dangott, L. J., Li, S., Kier, A. B., Schroeder, F. FABP1: a novel hepatic endocannabinoid and cannabinoid binding protein. Biochemistry 55: 5243-5255, 2016. [PubMed: 27552286] [Full Text: https://doi.org/10.1021/acs.biochem.6b00446]
Mukai, T., Egawa, M, Takeuchi, T., Yamashita, H., Kusuda, T. Silencing of FABP1 ameliorates hepatic steatosis, inflammation, and oxidative stress in mice with nonalcoholic fatty liver disease. FEBS Open Bio. 7: 1009-1016, 2017. Note: Electronic Article. [PubMed: 28680813] [Full Text: https://doi.org/10.1002/2211-5463.12240]
Rodriguez Sawicki, L., Bottasso Arias, N. M., Scaglia, N., Falomir Lockhart, L. J., Franchini, G. R., Storch, J., Corsico, B. FABP1 knockdown in human enterocytes impairs proliferation and alters lipid metabolism. Biochim. Biophys. Acta Molec. Cell Biol. Lipids 1862: 1587-1594, 2017. [PubMed: 28919479] [Full Text: https://doi.org/10.1016/j.bbalip.2017.09.006]
Sparkes, R. S., Mohandas, T., Heinzmann, C., Gordon, J. I., Klisak, I., Zollman, S., Sweetser, D. A., Ragunathan, L., Winokur, S., Lusis, A. J. Human fatty acid binding protein assignments: intestinal to 4q28-4q31 and liver to 2p11. (Abstract) Cytogenet. Cell Genet. 46: 697 only, 1987.
Storey, S. M., Huang, H., McIntosh, A. L., Martin, G. G., Kier, A. B., Schroeder, F. Impact of Fabp1/Scp-2/Scp-x gene ablation (TKO) on hepatic phytol metabolism in mice. J. Lipid Res. 58: 1153-1165, 2017. [PubMed: 28411199] [Full Text: https://doi.org/10.1194/jlr.M075457]
Sweetser, D. A., Birkenmeier, E. H., Klisak, I. J., Zollman, S., Sparkes, R. S., Mohandas, T., Lusis, A. J., Gordon, J. I. The human and rodent intestinal fatty acid binding protein genes: a comparative analysis of their structure, expression, and linkage relationships. J. Biol. Chem. 262: 16060-16071, 1987. [PubMed: 2824476]
Xu, H., Gajda, A. M., Zhou, Y. X., Panetta, C., Sifnakis, Z., Fatima, A., Henderson, G. C., Storch, J. Muscle metabolic reprogramming underlies the resistance of liver fatty acid-binding protein (LFABP)-null mice to high-fat feeding-induced decline in exercise capacity. J. Biol. Chem. 294: 15358-15372, 2019. [PubMed: 31451493] [Full Text: https://doi.org/10.1074/jbc.RA118.006684]