Tissue-specific Functions in the Fatty Acid-binding Protein Family
ABSTRACT The intracellular fatty acid-binding proteins (FABPs) are abundantly expressed in almost all tissues. They exhibit high affinity binding of a single long-chain fatty acid, with the exception of liver FABP, which binds two fatty acids or other hydrophobic molecules. FABPs have highly similar tertiary structures consisting of a 10-stranded antiparallel β-barrel and an N-terminal helix-turn-helix motif. Research emerging in the last decade has suggested that FABPs have tissue-specific functions that reflect tissue-specific aspects of lipid and fatty acid metabolism. Proposed roles for FABPs include assimilation of dietary lipids in the intestine, targeting of liver lipids to catabolic and anabolic pathways, regulation of lipid storage and lipid-mediated gene expression in adipose tissue and macrophages, fatty acid targeting to β-oxidation pathways in muscle, and maintenance of phospholipid membranes in neural tissues. The regulation of these diverse processes is accompanied by the expression of different and sometimes multiple FABPs in these tissues and may be driven by protein-protein and protein-membrane interactions.
- SourceAvailable from: Jean-Marc Alessandri
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- "Moreover, the expression profile of FABPs in cerebral cortex confirms that FABP5 and 7 were expressed in the brain mainly at the late embryonic stage  with an abundance level 10-times higher than that of other fatty acid transport proteins. This superiority , which persists until day 14 of lactation, is supposed to be required during brain development for AA and DHA channelling for phospholipid and membrane synthesis during proliferation/ differentiation of stem cells and neurite outgrowth  . "
ABSTRACT: Specific mechanisms for maintaining docosahexaenoic acid (DHA) concentration in brain cells but also transporting DHA from the blood across the blood-brain barrier (BBB) are not agreed upon. Our main objective was therefore to evaluate the level of gene expression of fatty acid transport and fatty acid binding proteins in the cerebral cortex and at the BBB level during the perinatal period of active brain DHA accretion, at weaning, and until the adult age. We measured by real time RT-PCR the mRNA expression of the different isoforms of fatty acid transport proteins (FATPs), long-chain acyl-CoA synthetases (ACSLs), fatty acid binding proteins (FABPs) and of the fatty acid transporter (FAT)/CD36 in cerebral cortex and isolated microvessels at embryonic day 18 (E18) and postnatal days 14, 21 and 60 (P14, P21 and P60, respectively) in rats receiving different n-3 PUFA dietary supplies (control, totally deficient or DHA-supplemented). In control rats, all the genes were expressed at the BBB level (P14 to P60), the mRNA levels of FABP5 and ACSL3 having the highest values. Age-dependent differences included a systematic decrease in the mRNA expressions between P14-P21 and P60 (2 to 3-fold), with FABP7 mRNA abundance being the most affected (10-fold). In the cerebral cortex, mRNA levels varied differently since FATP4, ACSL3 and ACSL6 and the three FABPs genes were highly expressed. There were no significant differences in the expression of the 10 genes studied in n-3 deficient or DHA-supplemented rats despite significant differences in their brain DHA content, suggesting that brain DHA uptake from the blood does not necessarily require specific transporters within cerebral endothelial cells and could, under these experimental conditions, be a simple passive diffusion process.Prostaglandins Leukotrienes and Essential Fatty Acids 11/2014; 91(5). DOI:10.1016/j.plefa.2014.07.004 · 1.98 Impact Factor
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- "These proteins are widely distributed throughout the body; they have distinct tissue distributions and exhibit a different degree of binding promiscuity. Due to their central role in lipid-mediated biological processes and systemic metabolic homeostasis  , iLBPs have been proposed as therapeutic targets against lipid-related disorders. "
ABSTRACT: Lipids are essential for many biological processes and crucial in the pathogenesis of several diseases. Intracellular lipid-binding proteins (iLBPs) provide mobile hydrophobic binding sites that allow hydrophobic or amphipathic lipid molecules to penetrate into and across aqueous layers. Thus iLBPs mediate the lipid transport within the cell and participate to a spectrum of tissue-specific pathways involved in lipid homeostasis. Structural studies have shown that iLBPs binding sites are inaccessible from the bulk, implying that substrate binding should involve a conformational change able to produce a ligand entry portal. Many studies have been reported in the last two decades on iLBPs indicating that their dynamics play a pivotal role in regulating ligand binding and targeted release. The ensemble of reported data has not been reviewed until today. This review is thus intended to summarise and possibly generalise the results up to now described, providing a picture which could help to identify the missing notions necessary to improve our understanding of the role of dynamics in iLBPs molecular recognition. Such notions would clarify the chemistry of lipid binding to iLBPs and set the basis for the development of new drugs.Biochimica et Biophysica Acta 04/2014; 1844(7). DOI:10.1016/j.bbapap.2014.04.011 · 4.66 Impact Factor
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- "An imbalance in the n-6/n-3-PUFA ratio may be a pathological factor in several neuropsychiatric disorders (Sakayori and Osumi, 2013). FABP3 levels are decreased in the brains of patients with Down syndrome and Alzheimer's disease (Cheon et al., 2003), which provides indirect evidence of a relationship between FABP3 and neurological functions and diseases (Storch and Thumser, 2010). These studies indicate that Fabp3 may have an important role in maintaining normal brain functions. "
ABSTRACT: Fatty acid-binding protein 3 (Fabp3) is an intracellular lipid trafficking protein that mediates energy metabolism and long-chain fatty acid-related signaling. Fabp3 is expressed in the spiral ganglion neurons and supporting cells of the organ of Corti. However, it is unclear what role Fabp3 plays in the cochlea. Here, we demonstrated that the ABR thresholds of young and aged Fabp3 knockout mice were unchanged compared with those of wild-type mice. Compared with the wild-type mice, the adult mutant mice demonstrated no differences in their vulnerability to acoustic overexposure. These results suggest that Fabp3 deficiency alone does not adversely affect hearing function.Neuroscience Research 04/2014; 81-82. DOI:10.1016/j.neures.2014.02.003 · 2.15 Impact Factor