ArticleThe Journal of biological chemistry2019
A ligand-induced structural change in fatty acid-binding protein 1 is associated with potentiation of peroxisome proliferator-activated receptor α agonists.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- TMEM135 deficiency prevents intestinal lipid accumulation by coordinating lipid uptake and oxidation through ELOVL6-mediated PPARα activation.Experimental & molecular medicine · 2026Article
- Abnormal lipid metabolism in senescent renal tubular cells in diabetic nephropathy.Cellular and molecular life sciences : CMLS · 2026Review
- Development of physiologically based liver distribution model that incorporates intracellular lipid partitioning and binding to fatty acid binding protein 1.The Journal of pharmacology and experimental therapeutics · 2026Article
- Development of Physiologically Based Liver Distribution Model that Incorporates Intracellular Lipid Partitioning and Binding to Fatty Acid Binding Protein 1 (FABP1).bioRxiv : the preprint server for biology · 2026Article
- Analysis of fatty acids concentration in the liver of rats with diet-induced obesity after bariatric surgery and a high-fat/high-sugar diet.Frontiers in physiology · 2026Article
- Inhibition of RACGAP1 sensitizes triple-negative breast cancer cells to ferroptosis by regulating CPT1A-dependent fatty acid metabolism.Journal of experimental & clinical cancer research : CR · 2025Article
- One anastomosis gastric bypass ameliorates diabetic nephropathy via regulating the GLP-1-mediated Sirt1/AMPK/PGC1α pathway.Clinical and experimental nephrology · 2024Article
- Multiplexed Native Mass Spectrometry Determination of Ligand Selectivity for Fatty Acid-Binding Proteins.ACS medicinal chemistry letters · 2024Article
- Muscle-building supplement β-hydroxy β-methylbutyrate stimulates the maturation of oligodendroglial progenitor cells to oligodendrocytes.Journal of neurochemistry · 2024Article
- Tardigrade secretory proteins protect biological structures from desiccation.Communications biology · 2024Article
- Article
- The Multifunctional Family of Mammalian Fatty Acid-Binding Proteins.Annual review of nutrition · 2023Review
- Impact of Intracellular Lipid Binding Proteins on Endogenous and Xenobiotic Ligand Metabolism and Disposition.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- The role of peroxisome proliferator-activated receptors (PPAR) in immune responses.Metabolism: clinical and experimental · 2021Review
- Monounsaturated Fatty Acids in Obesity-Related Inflammation.International journal of molecular sciences · 2020Review
- Small-Molecule Modulation of PPARs for the Treatment of Prevalent Vascular Retinal Diseases.International journal of molecular sciences · 2020Review
- Structural characterization of life-extending Caenorhabditis elegans Lipid Binding Protein 8.Scientific reports · 2019Article
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Authors and funding
15 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peroxisome proliferator-activated receptor α (PPARα) is a transcriptional regulator of lipid metabolism. GW7647 is a potent PPARα agonist that must reach the nucleus to activate this receptor. In cells expressing human fatty acid-binding protein 1 (FABP1), GW7647 treatment increases FABP1's nuclear localization and potentiates GW7647-mediated PPARα activation; GW7647 is less effective in cells that do not express FABP1. To elucidate the underlying mechanism, here we substituted residues in FABP1 known to dictate lipid signaling by other intracellular lipid-binding proteins. Substitutions of Lys-20 and Lys-31 to Ala in the FABP1 helical cap affected neither its nuclear localization nor PPARα activation. In contrast, Ala substitution of Lys-57, Glu-77, and Lys-96, located in the loops adjacent to the ligand-binding portal region, abolished both FABP1 nuclear localization and GW7647-induced PPARα activation but had little effect on GW7647-FABP1 binding affinity. Using solution NMR spectroscopy, we determined the WT FABP1 structure and analyzed the dynamics in the apo and GW7647-bound structures of both the WT and the K57A/E77A/K96A triple mutant. We found that GW7647 binding causes little change in the FABP1 backbone, but solvent exposes several residues in the loops around the portal region, including Lys-57, Glu-77, and Lys-96. These residues also become more solvent-exposed upon binding of FABP1 with the endogenous PPARα agonist oleic acid. Together with previous observations, our findings suggest that GW7647 binding stabilizes a FABP1 conformation that promotes its interaction with PPARα. We conclude that full PPARα agonist activity of GW7647 requires FABP1-dependent transport and nuclear localization processes.
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