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Fatty acid-binding protein

About: Fatty acid-binding protein is a research topic. Over the lifetime, 1721 publications have been published within this topic receiving 81530 citations. The topic is also known as: FABP.


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Book ChapterDOI
TL;DR: The crystal structure of LFABP contains two bound oleate molecules and provides the explanation for its unusual stoichiometry, which will bind hydrophobic molecules larger than the ligands which will associate with other iLBPs.
Abstract: The crystal and solution structures of all of the intracellular lipid binding proteins (iLBPs) reveal a common β-barrel framework with only small local perturbations. All existing evidence points to the binding cavity and a poorly delimited ‘portal’ region as defining the function of each family member. The importance of local structure within the cavity appears to be its influence on binding affinity and specificity for the lipid. The portal region appears to be involved in the regulation of ligand exchange. Within the iLBP family, liver fatty acid binding protein or LFABP, has the unique property of binding two fatty acids within its internalized binding cavity rather than the commonly observed stoichiometry of one. Furthermore, LFABP will bind hydrophobic molecules larger than the ligands which will associate with other iLBPs. The crystal structure of LFABP contains two bound oleate molecules and provides the explanation for its unusual stoichiometry. One of the bound fatty acids is completely internalized and has its carboxylate interacting with an arginine and two serines. The second oleate represents an entirely new binding mode with the carboxylate on the surface of LFABP. The two oleates also interact with each other. Because of this interaction and its inner location, it appears the first oleate must be present before the second more external molecule is bound.

49 citations

Journal ArticleDOI
TL;DR: Data characterized a functional promoter of the human aP2 gene; its in vitro pharmacological regulation in PPARγ-mediated reporter-gene assay may represent an interesting complement or an alternative to time-consuming procedures aiming at discriminating PPAR ligands with low lipogenic properties.
Abstract: Peroxisome proliferator-activated receptors (PPARs) regulate storage and catabolism of fats and carbohydrates. PPARgamma activity increases insulin sensitivity and adipocyte differentiation at the expense of adipogenesis and weight gain. The goal of this study was to 1) clone the promoter of the human adipocyte fatty acid binding protein (aP2) gene, namely fatty acid-binding protein-4, 2) characterize its pharmacological regulation, and 3) determine its putative predictability for adipogenesis. Among the selected PPAR agonists, rosiglitazone and pioglitazone displayed the highest maximal efficacy (E(max)) on reporter-gene assays in COS-7 cells cotransfected by either a galactosidase 4-response element-based or a human aP2 promoter-based Luc reporter vector, along with either chimeric or full-length human PPAR expression plasmids. The non-subtype-selective 2-(4-[2-(3-[2,4-difluorophenyl]-1-heptylureido)ethyl]phenoxy)-2-methyl-butyric acid (GW-2331) and the compounds [4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-propoxyl]phenoxy]-acetic acid (L-165041), (4-((2S,5S)-5-(2-(bis(phenylmethyl)amino)-2-oxoethyl)-2-heptyl-4-oxo-3-thiazolidinyl)butyl)-benzoic acid (GW-0072), and indomethacin behaved as partial agonists relative to pioglitazone in full-length human aP2-PPARgamma2. Beyond their partial PPARgamma agonist properties, these compounds elicited a lower maximal up-regulation of mouse aP2 mRNA in 3T3-L1 adipocytes as compared with pioglitazone; these properties paralleled a time-dependent increase in neutral lipids. By contrast, the selective PPARalpha agonist 2,2-dichloro-12-(4-chlorophenyl)dodecanoic acid (BM-17.0744) neither stimulated the human aP2-PPARalpha promoter reporter-gene assay, thus demonstrating a specific interaction between PPARgamma and the aP2 promoter, nor affected lipogenesis in 3T3-L1 cells. Altogether, these data characterized a functional promoter of the human aP2 gene; its in vitro pharmacological regulation in PPARgamma-mediated reporter-gene assay may represent an interesting complement or an alternative to time-consuming procedures aiming at discriminating PPAR ligands with low lipogenic properties.

49 citations

Journal ArticleDOI
TL;DR: A cytosolic protein, able to facilitate intermembrane movements of phospholipids in vitro, has been purified to homogeneity from sunflower seedlings and is able to bind oleoyl-CoA, as shown by FPLC chromatography.
Abstract: A cytosolic protein, able to facilitate intermembrane movements of phospholipids in vitro, has been purified to homogeneity from sunflower seedlings. This protein, which has the properties of a lipid-transfer protein (LTP), is also able to bind oleoyl-CoA, as shown by FPLC chromatography. This finding, in addition to previous observations suggesting that a lipid-transfer protein from spinach leaves can bind oleic acid and that oat seedlings contain a fatty acid-binding protein with similar features than lipid transfer proteins, provides a clear demonstration that plant cells contain bifunctional fatty acid/lipid transfer proteins. These proteins can play an active role in fatty acid metabolism which involves movements of oleyl-CoA between intracellular membranes.

49 citations

Journal ArticleDOI
TL;DR: Investigation of molecular mechanisms involved in tumor-promoting activity of C-FABP has established that there is a fatty acid-initiated signaling pathway leading to malignant progression of prostatic cancer cells.
Abstract: Cutaneous fatty acid-binding protein (C-FABP), a cancer promoter and metastasis inducer, is overexpressed in the majority of prostatic carcinomas Investigation of molecular mechanisms involved in tumor-promoting activity of C-FABP has established that there is a fatty acid-initiated signaling pathway leading to malignant progression of prostatic cancer cells Increased C-FABP expression plays an important role in this novel signaling pathway Thus, when C-FABP expression is increased, excessive amounts of fatty acids are transported into the nucleus where they act as signaling molecules to stimulate their nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) The activated PPARγ then modulates the expression of its downstream target regulatory genes, which eventually lead to enhanced tumor expansion and aggressiveness caused by an overgrowth of cells with reduced apoptosis and an increased angiogenesis

49 citations

Journal ArticleDOI
TL;DR: More experimental work, using a variety of study samples and complementary approaches, is necessary before advocating routine testing of FABP2 genotype in people in order to determine their potential responsiveness to various dietary interventions, such as increased dietary soluble fiber.

48 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202368
202272
202142
202044
201950
201851