Fatty acid-binding proteins
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PROVIDER: S-EPMC2884656 | biostudies-literature | 2009 Nov
REPOSITORIES: biostudies-literature
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Project description:Fatty acid binding proteins (FABPs) carry fatty acids (FAs) and other lipids in the cellular environment, and are thus involved in processes such as FA uptake, transport, and oxidation. These proteins bind either one or two ligands in a binding site, which appears to be inaccessible from the bulk. Thus, the entry of the substrate necessitates a conformational change, whose nature is still unknown. A possible description of the ligand binding process is given by the portal hypothesis, which suggests that the FA enters the protein through a dynamic area known as the portal region. On the other hand, recent simulations of the adipocyte lipid binding protein (ALBP) suggested a different entry site (the alternative portal). In this article, we discuss molecular dynamics simulations of the apo-intestinal-FABP (I-FABP) in the presence of palmitate molecule(s) in the simulation box. The simulations were carried out to study whether the FA can enter the protein during the simulations (as in the ALBP) and where the ligand entry site is (the portal region, the alternative portal or a different domain). The analysis of the simulations revealed a clear difference between the ALBP and the I-FABP. In the latter case, the palmitate preferentially adsorbed to the portal region, which was more mobile than the rest of the protein. However, no ligand entry was observed in the multi-nanosecond-long simulations, in contrast to ALBP. These findings suggest that, although the main structural motif of the FABPs is common, the fine details of each individual protein structure grossly modulate its reactivity.
| S-EPMC1367305 | biostudies-literature
Project description:The mammalian FA-binding proteins (FABPs) bind long-chain FA with high affinity. The large number of FABP types is suggestive of distinct functions in specific tissues. Multiple experimental approaches have shown that individual FABPs possess both unique and overlapping functions, some of which are based on specific elements in the protein structure. Although FA binding affinities for all FABPs tend to correlate directly with FA hydrophobicity, structure-function studies indicate that subtle three-dimensional changes that occur upon ligand binding may promote specific protein-protein or protein-membrane interactions that ultimately determine the function of each FABP. The conformational changes are focused in the FABP helical/portal domain, a region that was identified by in vitro studies to be vital for the FA transport properties of the FABPs. Thus, the FABPs modulate intracellular lipid homeostasis by regulating FA transport in the nuclear and extra-nuclear compartments of the cell; in so doing, they also impact systemic energy homeostasis.
| S-EPMC2674722 | biostudies-literature
Project description:Fatty acid-binding proteins (FABPs) are small lipid-binding proteins abundantly expressed in tissues that are highly active in fatty acid (FA) metabolism. Ten mammalian FABPs have been identified, with tissue-specific expression patterns and highly conserved tertiary structures. FABPs were initially studied as intracellular FA transport proteins. Further investigation has demonstrated their participation in lipid metabolism, both directly and via regulation of gene expression, and in signaling within their cells of expression. There is also evidence that they may be secreted and have functional impact via the circulation. It has also been shown that the FABP ligand binding repertoire extends beyond long-chain FAs and that their functional properties also involve participation in systemic metabolism. This article reviews the present understanding of FABP functions and their apparent roles in disease, particularly metabolic and inflammation-related disorders and cancers.
| S-EPMC10909404 | biostudies-literature
Project description:Phylogenetic analysis of avian and other vertebrate fatty acid binding proteins (FABPs) supported the hypothesis that several gene duplications within this family occurred prior to the most recent common ancestor (MRCA) of tetrapods and bony fishes. The chicken genome encodes two liver-expressed FABPs: (1) L-FABP or FABP1; and (2) Lb-FABP. We propose that the latter be designated FABP10, because in our phylogenetic analysis it clustered with zebrafish FABP10. Bioinformatic analysis of across-tissue gene expression patterns in the chicken showed some congruence with phylogenetic relationships. On the basis of expression, chicken FABP genes seemed to form two major groups: (1) a cluster of genes many of which showed predominant expression in the digestive system (FABP1, FABP2, FABP6, FABP10, RBP1, and CRABP1); and (2) a cluster of genes most of which had predominant expression in tissues other than those of the digestive system, including muscle and the central nervous system (FABP3, FABP4, FABP5, FABP7, and PMP2). Since these clusters corresponded to major clusters in the phylogenetic tree as well, it seems a plausible hypothesis that the earliest duplication in the vertebrate FABP family led to the divergence of a gut-specialized gene from a gene expressed mainly in nervous and muscular systems. Data on gene expression in livers of two lines of chickens selected for high growth and low growth showed differences between FABP1 and FABP10 expressions in the liver, supporting the hypothesis of functional divergence between the two chicken liver-expressed FABPs related to food intake.
| S-EPMC4009381 | biostudies-literature
Project description:Inflammation plays a key role in the pathogenesis of bronchopulmonary dysplasia (BPD). Fatty acid-binding proteins (FABPs) 4 and 5 regulate the inflammatory activity of macrophages. Whether FABPs 4 and 5 could play a role in the pathogenesis of BPD via the promotion of macrophage inflammatory activity is unknown. This study sought to examine whether the expression levels of FABP4 and FABP5 were altered in bronchoalveolar lavage fluid and lung tissue in a baboon model of BPD. This study also sought to characterize the cell types that express these proteins. Real-time PCR, immunoblotting, immunohistochemistry, and double immunofluorescence were used to examine the expression of FABPs in samples of BPD. Morphometric analysis was used to quantify FABP4-positive peribronchial blood vessels in lung sections. FABP4 was primarily expressed in macrophages in samples of BPD. In addition, FABP4 was expressed in the endothelial cells of blood vessels in peribronchial areas and the vasa vasorum, but not in the alveolar vasculature in samples of BPD. FABP4 concentrations were significantly increased in lungs and bronchoalveolar lavage fluid samples with BPD. An increased density of FABP4-positive peribronchial blood vessels was evident in both baboon and human BPD sections. FABP5 was expressed in several cell types, including alveolar epithelial cells and macrophages. FABP5 concentrations did not show any significant alterations in BPD. In conclusion, FABP4 but not FABP5 levels are increased in BPD. FABP4 is differentially expressed in endothelial cells of the bronchial microvasculature, which demonstrates a previously unrecognized expansion in BPD.
| S-EPMC3175587 | biostudies-literature
Project description:Fatty-acid-binding proteins (FABPs) serve a crucial role in the metabolism and transport of fatty acids and other hydrophobic ligands as an intracellular protein family. They are also recognized as a critical mediator in the inflammatory and ischemic pathways. FABPs are found in a wide range of tissues and organs, allowing them to contribute to various disease/injury developments that have not been widely discussed. We have collected and analyzed research journals that have investigated the role of FABPs in various diseases. Through this review, we discuss the findings on the potential of FABPs as biomarkers for various diseases in different tissues and organs, looking at their expression levels and their roles in related diseases according to available literature data. FABPs have been reported to show significantly increased expression levels in various tissues and organs associated with metabolic and inflammatory diseases. Therefore, FABPs are a promising novel biomarker that needs further development to optimize disease diagnosis and prognosis methods along with previously discovered markers.
| S-EPMC10741572 | biostudies-literature
Project description:ObjectiveThis study identifies single-nucleotide polymorphisms (SNP) or gene combinations that affect the flavor and quality of Korean cattle (Hanwoo) by using the SNP Harvester method.MethodsFour economic traits (oleic acid [C18:1], saturated fatty acids), monounsaturated fatty acids, and marbling score) were adjusted for environmental factors in order to focus solely on genetic effects. The SNP Harvester method was used to investigate gene combinations (two-way gene interactions) associated with these economic traits. Further, a multifactor dimensionality reduction method was used to identify superior genotypes in gene combinations.ResultsTable 3 to 4 show the analysis results for differences between superior genotypes and others for selected major gene combinations using the multifactor dimensionality reduction method. Environmental factors were adjusted for in order to evaluate only the genetic effect. Table 5 shows the adjustment effect by comparing the accuracy before and after correction in two-way gene interactions.ConclusionThe g.3977-325 T>C and (g.2988 A>G, g.3977-325 T>C) combinations of fatty acid-binding protein4 were the superior gene, and the superior genotype combinations across all economic traits were the CC genotype at g.3977-325 T>C and the AACC, GACC, GGCC genotypes of (g.2988 A>G, g.3977-325 T>C).
| S-EPMC5205601 | biostudies-literature
Project description:Two fatty acid binding proteins, MvFABPa and MvFABPb were identified in the parasite Mesocestoides vogae (Platyhelmithes, Cestoda). Fatty acid binding proteins are small intracellular proteins whose members exhibit great diversity. Proteins of this family have been identified in many organisms, of which Platyhelminthes are among the most primitive. These proteins have particular relevance in flatworms since de novo synthesis of fatty acids is absent. Fatty acids should be captured from the media needing an efficient transport system to uptake and distribute these molecules. While HLBPs could be involved in the shuttle of fatty acids to the surrounding host tissues and convey them into the parasite, FABPs could be responsible for the intracellular trafficking. In an effort to understand the role of MvFABPs in fatty acid transport of M. vogae larvae, we analysed the intracellular localization of both MvFABPs and the co-localization with in vivo uptake of fatty acid analogue BODIPY FL C16. Immunohistochemical studies on larvae sections using specific antibodies, showed a diffuse cytoplasmic distribution of each protein with some expression in nuclei and mitochondria. MvFABPs distribution was confirmed by mass spectrometry identification from 2D-electrophoresis of larvae subcellular fractions. This work is the first report showing intracellular distribution of MvFABPs as well as the co-localization of these proteins with the BODIPY FL C16 incorporated from the media. Our results suggest that fatty acid binding proteins could target fatty acids to cellular compartments including nuclei. In this sense, M. vogae FABPs could participate in several cellular processes fulfilling most of the functions attributed to vertebrate's counterparts.
| S-EPMC4210247 | biostudies-literature
Project description:Celiac disease (CD) is an immune-mediated enteropathy that develops in genetically susceptible individuals following exposure to dietary gluten. Severe changes at the intestinal mucosa observed in untreated CD patients are linked to changes in the level and in the pattern of expression of different genes. Fully differentiated epithelial cells express two isoforms of fatty acid binding proteins (FABPs): intestinal and liver, IFABP and LFABP, respectively. These proteins bind and transport long chain fatty acids and also have other important biological roles in signaling pathways, particularly those related to PPARγ and inflammatory processes. Herein, we analyze the serum levels of IFABP and characterize the expression of both FABPs at protein and mRNA level in small intestinal mucosa in severe enteropathy and normal tissue. As a result, we observed higher levels of circulating IFABP in untreated CD patients compared with controls and patients on gluten-free diet. In duodenal mucosa a differential FABPs expression pattern was observed with a reduction in mRNA levels compared to controls explained by the epithelium loss in severe enteropathy. In conclusion, we report changes in FABPs' expression pattern in severe enteropathy. Consequently, there might be alterations in lipid metabolism and the inflammatory process in the small intestinal mucosa.
| S-EPMC4540995 | biostudies-literature
Project description:Fatty acid-binding proteins (FABPs) regulate the intracellular dynamics of fatty acids, mediate lipid metabolism and participate in signaling processes. However, the therapeutic efficacy of targeting FABPs as novel therapeutic targets for cerebral ischemia is not well established. Previously, we synthesized a novel FABP inhibitor, i.e., FABP ligand 6 [4-(2-(5-(2-chlorophenyl)-1-(4-isopropylphenyl)-1H-pyrazol-3-yl)-4-fluorophenoxy)butanoic acid] (referred to here as MF6). In this study, we analyzed the ability of MF6 to ameliorate transient middle cerebral artery occlusion (tMCAO) and reperfusion-induced injury in mice. A single MF6 administration (3.0 mg/kg, per os) at 0.5 h post-reperfusion effectively reduced brain infarct volumes and neurological deficits. The protein-expression levels of FABP3, FABP5 and FABP7 in the brain gradually increased after tMCAO. Importantly, MF6 significantly suppressed infarct volumes and the elevation of FABP-expression levels at 12 h post-reperfusion. MF6 also inhibited the promotor activity of FABP5 in human neuroblastoma cells (SH-SY5Y). These data suggest that FABPs elevated infarct volumes after ischemic stroke and that inhibiting FABPs ameliorated the ischemic injury. Moreover, MF6 suppressed the inflammation-associated prostaglandin E2 levels through microsomal prostaglandin E synthase-1 expression in the ischemic hemispheres. Taken together, the results imply that the FABP inhibitor MF6 can potentially serve as a neuroprotective therapeutic for ischemic stroke.
| S-EPMC8150391 | biostudies-literature