Showing papers on "Fatty acid-binding protein published in 2008"

The emerging functions and mechanisms of mammalian fatty acid-binding proteins

Abstract: Fatty acid-binding proteins (FABPs) are abundant intracellular proteins that bind long-chain fatty acids with high affinity. Nine separate mammalian FABPs have been identified, and their tertiary structures are highly conserved. The FABPs have unique tissue-specific distributions that have long suggested functional differences among them. In the last decade, considerable progress has been made in understanding the specific functions of the FABPs and, in some cases, their mechanisms of action at the molecular level. The FABPs appear to be involved in the extranuclear compartments of the cell by trafficking their ligands within the cytosol via interactions with organelle membranes and specific proteins. Several members of the FABP family have been shown to function directly in the regulation of cognate nuclear transcription factor activity via ligand-dependent translocation to the nucleus. This review will focus on these emerging functions and mechanisms of the FABPs, highlighting the unique functional properties of each as well as the similarities among them.

Role of Fatty Acid Binding Proteins and Long Chain Fatty Acids in Modulating Nuclear Receptors and Gene Transcription

Abstract: Abnormal energy regulation may significantly contribute to the pathogenesis of obesity, diabetes mellitus, cardiovascular disease, and cancer. For rapid control of energy homeostasis, allosteric and posttranslational events activate or alter activity of key metabolic enzymes. For longer impact, transcriptional regulation is more effective, especially in response to nutrients such as long chain fatty acids (LCFA). Recent advances provide insights into how poorly water-soluble lipid nutrients [LCFA; retinoic acid (RA)] and their metabolites (long chain fatty acyl Coenzyme A, LCFA-CoA) reach nuclei, bind their cognate ligand-activated receptors, and regulate transcription for signaling lipid and glucose catabolism or storage: (i) while serum and cytoplasmic LCFA levels are in the 200 μM–mM range, real-time imaging recently revealed that LCFA and LCFA-CoA are also located within nuclei (nM range); (ii) sensitive fluorescence binding assays show that LCFA-activated nuclear receptors [peroxisome proliferator-activated receptor-α (PPARα) and hepatocyte nuclear factor 4α (HNF4α)] exhibit high affinity (low nM Kds) for LCFA (PPARα) and/or LCFA-CoA (PPARα, HNF4α)—in the same range as nuclear levels of these ligands; (iii) live and fixed cell immunolabeling and imaging revealed that some cytoplasmic lipid binding proteins [liver fatty acid binding protein (L-FABP), acyl CoA binding protein (ACBP), cellular retinoic acid binding protein-2 (CRABP-2)] enter nuclei, bind nuclear receptors (PPARα, HNF4α, CRABP-2), and activate transcription of genes in fatty acid and glucose metabolism; and (iv) studies with gene ablated mice provided physiological relevance of LCFA and LCFA-CoA binding proteins in nuclear signaling. This led to the hypothesis that cytoplasmic lipid binding proteins transfer and channel lipidic ligands into nuclei for initiating nuclear receptor transcriptional activity to provide new lipid nutrient signaling pathways that affect lipid and glucose catabolism and storage.

Contribution of FAT/CD36 to the regulation of skeletal muscle fatty acid oxidation: an overview.

Abstract: Long chain fatty acids (LCFAs) are an important substrate for ATP production within the skeletal muscle The process of LCFA delivery from adipose tissue to muscle mitochondria involves many regulatory steps Recently, it has been recognized that LCFA oxidation is not only dependent on LCFA delivery to the muscle, but also on regulatory steps within the muscle Increasing selected fatty acid binding proteins/transporters on the plasma membrane facilitates a very rapid LCFA increase into the muscle, independent of any changes in LCFA delivery to the muscle Such a mechanism of LCFA transporter translocation is activated by muscle contraction Intramuscular triacylglycerols may also be hydrolysed to provide fatty acids for mitochondrial oxidation, particularly during exercise, when hormone-sensitive lipase and other enzymes are activated Mitochondrial LCFA entry is also highly regulated This however does not involve only the malonyl CoA carnitine palmitoyltransferase-I (CPTI) axis Exercise-induced fatty acid entry into mitochondria is also regulated by at least one of the proteins (FAT/CD36) that also regulates plasma membrane fatty acid transport Among individuals, differences in mitochondrial fatty acid oxidation appear to be correlated with the content of mitochondrial CPTI and FAT/CD36 This paper provides a brief overview of mechanisms that regulate LCFA uptake and oxidation in skeletal muscle during exercise and in obesity We focus largely on our own work on FAT/CD36, which contributes to regulating, in a coordinated fashion, LCFA uptake across the plasma membrane and the mitochondrial membrane Very little is known about the roles of FATP1-6 on fatty acid transport in skeletal muscle

Polyunsaturated fatty acid modulation of voltage-gated ion channels.

Abstract: Arachidonic acid (AA) was found to inhibit the function of whole-cell voltage-gated (VG) calcium currents nearly 16 years ago. There are now numerous examples demonstrating that AA and other polyunsaturated fatty acids (PUFAs) modulate the function of VG ion channels, primarily in neurons and muscle cells. We will review and extract some common features about the modulation by PUFAs of VG calcium, sodium, and potassium channels and discuss the impact of this modulation on the excitability of neurons and cardiac myocytes. We will describe the fatty acid nature of the membrane, how fatty acids become available to function as modulators of VG channels, and the physiologic importance of this type of modulation. We will review the evidence for molecular mechanisms and assess our current understanding of the structural basis for modulation. With guidance from research on the structure of fatty acid binding proteins, the role of lipids in gating mechanosensitive (MS) channels, and the impact of membrane lipid composition on membrane-embedded proteins, we will highlight some avenues for future investigations.

Fatty acid binding protein: localization and functional significance in the brain

Abstract: Long chain fatty acids are important nutrients for brain development and function. However, the molecular basis of their actions in the brain is still to be clarified. Fatty acid-binding proteins (FABPs) belong to the multigene family of the intracellular lipid-binding protein. FABPs bind to long chain fatty acids, being involved in the promotion of cellular uptake and transport of fatty acids, the targeting of fatty acids to specific metabolic pathways, and the regulation of gene expression. FABPs are widely expressed in mammalian tissues, with distinct expression patterns for the individual protein. Although FABPs have been implicated to serve as regulators in systemic cellular metabolic pathways, recent studies have demonstrated the ability of FABPs to regulate functions of the brain, one of the most fat-enriched tissues in the body. This review summarizes the localization of FABPs in the brain, and recent progress in elucidating the function of FABPs in the brain.

Differential gene expression of fatty acid binding proteins during porcine adipogenesis

Abstract: Four different subtypes of fatty acid binding proteins i.e. liver-type FABP1, heart/muscle-type FABP3, adipocyte-type FABP4 and epithelial/epidermal-type FABP5 are expressed in adipose tissue. However, only the regulatory role of FABP4 in adipogenesis has been thoroughly investigated. To increase the knowledge on possible roles of these FABP subtypes in preadipocyte differentiation, gene expression patterns were examined during adipogenesis in pig (Sus scrofa). FABP1 expression was induced in proliferating cells, whereas FABP3, FABP4 and FABP5 expression increased throughout preadipocyte differentiation. Interestingly, the FABP4 and FABP5 expression increased early in the differentiation, followed by FABP3 later in the differentiation process. This indicates a role of FABP4 and FABP5 in intracellular fatty acid transport during initiation of differentiation, whereas, FABP3 likely is involved in the transport of fatty acids during intermediate stages of adipogenesis. In this study we demonstrate that FABP3, FABP4 and FABP5 expression is correlated with that of the peroxisome proliferator-activated receptors alpha and gamma (PPARA and PPARG). Altogether, this suggests a role of FABP1 during cell proliferation, whereas a coordinated expression of FABP3, FABP4 and FABP5 together with that of PPARA, PPARG1 and PPARG2 might be critical for the metabolic regulation during porcine adipogenesis.

Characterization of the drug binding specificity of rat liver fatty acid binding protein.

Abstract: Liver-fatty acid binding protein (L-FABP) is found in high levels in enterocytes and is involved in the cytosolic solubilization of fatty acids during fat absorption. In the current studies, the interaction of L-FABP with a range of lipophilic drugs has been evaluated to explore the potential for L-FABP to provide an analogous function during the absorption of lipophilic drugs. Binding affinity for L-FABP was assessed by displacement of a fluorescent marker, 1-anilinonaphthalene-8-sulfonic acid (ANS), and the binding site location was determined via nuclear magnetic resonance chemical shift perturbation studies. It was found that the majority of drugs bound to L-FABP at two sites, with the internal site generally having a higher affinity for the compounds tested. Furthermore, in contrast to the interaction of L-FABP with fatty acids, it was demonstrated that a terminal carboxylate is not required for specific binding of lipophilic drugs at the internal site of L-FABP.

Expression of cell adhesion proteins and proteins related to angiogenesis and fatty acid metabolism in benign, atypical, and anaplastic meningiomas

Abstract: Most meningiomas are benign tumours of arachnoidal origin, although a small number have high proliferative rates and invasive properties which complicate complete surgical resection and are associated with increased recurrence rates. Few prognostic indicators exist for meningiomas and further research is necessary to identify factors that influence tumour invasion, oedema and recurrence. Paraffin sections from 25 intracranial meningiomas were analysed for expression of the proteins vascular endothelial growth factor (VEGF), VEGF receptors Flt1 and Flk1, E-cadherin, metalloproteinases 2 and 9 (MMP2, MMP9), CD44, receptor for hyaluronic acid-mediated motility (RHAMM), hyaluronic acid (HA), CD45, cyclooxygenase 2 (COX2), brain fatty acid binding protein (BFABP), Ki67, and proliferating cell nuclear antigen (PCNA). Correlations among protein expression were found for several markers of proliferation (Ki67, PCNA, MI) and microvessel density (MVD). COX2 expression increased with increasing with tumour grade and correlated with Ki67, PCNA, MI, MVD, and BFABP. BFABP expression also correlated with Ki67 and PCNA expression. Relationships were also identified among angiogenic factors (VEGF, Flt1, Flk1) and proliferation markers. Oedema was found to correlate with MMP9 expression and MMP9 also correlated with proliferation markers. No correlations were found for MMP2, E-cadherin, or CD44 in meningiomas. In conclusion Ki67, PCNA, MI, MVD, BFABP, and COX2 were significantly correlated with meningioma tumour grade and with each other. These findings, by correlating both intracellular fatty acid transport and eicosanoid metabolism with tumour proliferation, as determined by Ki67 labelling and mitotic index, suggest fatty acids are involved in the progression of meningiomas.

Cellular retinol-binding protein type III is a PPARγ target gene and plays a role in lipid metabolism

Abstract: Cellular retinol-binding protein (CRBP) type III (CRBP-III) belongs to the family of intracellular lipid-binding proteins, which includes the adipocyte-binding protein aP2. In the cytosol, CRBP-III binds retinol, the precursor of retinyl ester and the active metabolite retinoic acid. The goal of the present work is to understand the regulation of CRBP-III expression and its role in lipid metabolism. Using EMSAs, luciferase reporter assays, and chromatin immunoprecipitation assays, we found that CRBP-III is a direct target of peroxisome proliferator-activated receptor-γ (PPARγ). Moreover, CRBP-III expression was induced in adipose tissue of mice after treatment with the PPARγ agonist rosiglitazone. To examine a potential role of CRBP-III in regulating lipid metabolism in vivo, CRBP-III-deficient (C-III-KO) mice were maintained on a high-fat diet (HFD). Hepatic steatosis was decreased in HFD-fed C-III-KO compared with HFD-fed wild-type mice. These differences were partly explained by decreased serum free fatty acid levels and decreased free fatty acid efflux from adipose tissue of C-III-KO mice. In addition, the lack of CRBP-III was associated with reduced food intake, increased respiratory energy ratio, and altered body composition, with decreased adiposity and increased lean body mass. Furthermore, expression of genes involved in mitochondrial fatty acid oxidation in brown adipose tissue was increased in C-III-KO mice, and C-III-KO mice were more cold tolerant than wild-type mice fed an HFD. In summary, we demonstrate that CRBP-III is a PPARγ target gene and plays a role in lipid and whole body energy metabolism.

Proteomic analysis for inhibitory effect of chitosan oligosaccharides on 3T3-L1 adipocyte differentiation.

Abstract: In the present study, we performed a differential proteomic analysis using 2-DE combined with MS to clarify the molecular mechanism for the suppressive effect of chitosan oligosaccharides (CO) during differentiation of adipocyte 3T3-L1. Cell differentiation was significantly inhibited by CO at the concentration of 4 mg/mL. Protein mapping of adipocyte homogenates by 2-DE revealed that numerous protein spots were differentially altered in response to CO treatment. Out of 50 identified proteins showing significant alterations, six were up-regulated and 44 were down-regulated by CO treatment in comparison to control mature adipocytes. Among them, most of the proteins are associated with lipid metabolism, cytoskeleton, and redox regulation, in which the levels of farnesyl diphosphate synthetase (FDS), dedicator of cytokinesis 9 (DOCK9), and chloride intracellular channel 1 (CLIC1) were significantly reduced (.two-fold) with CO treatment. These results have not previously been examined in the context of adipogenesis, and thus can be used as novel biomarkers. Taken together with immunoblot analysis, it was concluded that the inhibitory effect of CO on adipocyte differentiation was mediated by C/EBPa and PPARg pathway through significant downregulations of important adipogenic molecules such as fatty acid binding protein and glucose transporter 4.

The intestine as source of cytotoxic mediators in shock: free fatty acids and degradation of lipid-binding proteins.

Abstract: Shock and multiple organ failure remain primary causes of late-stage morbidity and mortality in victims of trauma. During shock, the intestine is subject to extensive cell death and is the source of inflammatory factors that cause multiorgan failure. We (34) showed previously that ischemic, but not nonischemic, small intestines and pancreatic protease digested homogenates of normal small intestine can generate cytotoxic factors capable of killing naive cells within minutes. Using chloroform/methanol separation of rat small intestine homogenates into lipid fractions and aqueous and sedimented protein fractions and measuring cell death caused by those fractions, we found that the cytotoxic factors are lipid in nature. Recombining the lipid fraction with protein fractions prevented cell death, except when homogenates were protease digested. Using a fluorescent substrate, we found high levels of lipase activity in intestinal homogenates and cytotoxic levels of free fatty acids. Addition of albumin, a lipid binding protein, prevented cell death, unless the albumin was previously digested with protease. Homogenization of intestinal wall in the presence of the lipase inhibitor orlistat prevented cell death after protease digestion. In vivo, orlistat plus the protease inhibitor aprotinin, administered to the intestinal lumen, significantly improved survival time compared with saline in a splanchnic arterial occlusion model of shock. These results indicate that major cytotoxic mediators derived from an intestine under in vitro conditions are free fatty acids. Breakdown of free fatty acid binding proteins by proteases causes release of free fatty acids to act as powerful cytotoxic mediators.

Brain fatty acid binding protein (Fabp7) is diurnally regulated in astrocytes and hippocampal granule cell precursors in adult rodent brain.

Abstract: Brain fatty acid binding protein (Fabp7), which is important in early nervous system development, is expressed in astrocytes and neuronal cell precursors in mature brain. We report here that levels of Fabp7 mRNA in adult murine brain change over a 24 hour period. Unlike Fabp5, a fatty acid binding protein that is expressed widely in various cell types within brain, RNA analysis revealed that Fabp7 mRNA levels were elevated during the light period and lower during dark in brain regions involved in sleep and activity mechanisms. This pattern of Fabp7 mRNA expression was confirmed using in situ hybridization and found to occur throughout the entire brain. Changes in the intracellular distribution of Fabp7 mRNA were also evident over a 24 hour period. Diurnal changes in Fabp7, however, were not found in postnatal day 6 brain, when astrocytes are not yet mature. In contrast, granule cell precursors of the subgranular zone of adult hippocampus did undergo diurnal changes in Fabp7 expression. These changes paralleled oscillations in Fabp7 mRNA throughout the brain suggesting that cell-coordinated signals likely control brain-wide Fabp7 mRNA expression. Immunoblots revealed that Fabp7 protein levels also underwent diurnal changes in abundance, with peak levels occurring in the dark period. Of clock or clock-regulated genes, the synchronized, global cycling pattern of Fabp7 expression is unique and implicates glial cells in the response or modulation of activity and/or circadian rhythms.

Liver fatty acid-binding protein gene-ablated female mice exhibit increased age-dependent obesity.

Abstract: Previous work conducted in our laboratory suggested a role for liver fatty acid-binding protein (L-FABP) in obesity that develops in aging female L-FABP gene-ablated (-/-) mice. To examine this possibility in more detail, cohorts of wild-type (+/+) and L-FABP (-/-) female mice were fed a standard, low-fat, nonpurified rodent diet for up to 18 mo. Various obesity-related parameters were examined, including body weight and fat and lean tissue mass. Obesity in (-/-) mice was associated with increased expression of nuclear receptors that induce PPARalpha (e.g. hepatocyte nuclear factor 1alpha, genotype effect) and of PPARalpha-regulated proteins involved in uptake of free (lipoprotein lipase and fatty acid transport protein, genotype, and/or age effect) and esterified (scavenger receptor class B type 1, genotype effect) long-chain fatty acids (LCFA). Hepatic total lipid and neutral lipid levels were not affected by age or genotype, consistent with absence of gross and histologic steatosis. There was increased mRNA expression of liver proteins involved in LCFA oxidation [mitochondrial 3-oxoacyl-CoA thiolase (genotype effect) and butyryl-CoA dehydrogenase (genotype and/or age effect)], increased expression of LCFA esterification enzymes [glycerol-3-phosphate acyltransferase (age x genotype effect) and acyl-CoA:cholesterol acyltransferase-2 (genotype and/or age effect)], and increased expression of proteins involved in intracellular transfer and secretion of esterified LCFA [liver microsomal triacylglycerol transfer protein (genotype effect), serum apolipoprotein (apo) B (genotype or age effect), and liver apoB (age and age x genotype effect)]. The data support a working model in which obesity development in these mice results from shifts toward reduced energy expenditure and/or more efficient energy uptake in the gut.

Proteomic analysis of fructose-induced fatty liver in hamsters

Abstract: High fructose consumption is associated with the development of fatty liver and dyslipidemia with poorly understood mechanisms. We used a matrix-assisted laser desorption/ionization-based proteomics approach to define the molecular events that link high fructose consumption to fatty liver in hamsters. Hamsters fed high-fructose diet for 8 weeks, as opposed to regular-chow-fed controls, developed hyperinsulinemia and hyperlipidemia. High-fructose-fed hamsters exhibited fat accumulation in liver. Hamsters were killed, and liver tissues were subjected to matrix-assisted laser desorption/ionization-based proteomics. This approach identified a number of proteins whose expression levels were altered by >2-fold in response to high fructose feeding. These proteins fall into 5 different categories including (1) functions in fatty acid metabolism such as fatty acid binding protein and carbamoyl-phosphate synthase; (2) proteins in cholesterol and triglyceride metabolism such as apolipoprotein A-1 and protein disulfide isomerase; (3) molecular chaperones such as GroEL, peroxiredoxin 2, and heat shock protein 70, whose functions are important for protein folding and antioxidation; (4) enzymes in fructose catabolism such as fructose-1,6-bisphosphatase and glycerol kinase; and (5) proteins with housekeeping functions such as albumin. These data provide insight into the molecular basis linking fructose-induced metabolic shift to the development of metabolic syndrome characterized by hepatic steatosis and dyslipidemia.

Albumin as fatty acid transporter

Abstract: Fatty acids play critical roles in mammalian energy metabolism. Moreover, they are important substrates for the synthesis of membrane phospholipids and biologically active compounds like eicosanoids and leukotrienes. Because of their low solubility in aqueous solutions such as blood plasma and interstitial fluid, fatty acids are in need of binding proteins to increase their concentration in vascular and interstitial compartments. Albumin acts as main fatty acid binding protein in extracellular fluids. Plasma albumin possesses about 7 binding sites for fatty acids with moderate to high affinity, enhancing the concentration of fatty acids by a several orders of magnitude. Despite the high affinity of albumin for fatty acids, uptake of fatty acids by parenchymal cells such as skeletal and cardiac myocytes seems not to be hampered by albumin. In contrast, experimental findings suggest that albumin may facilitate the uptake of fatty acids by organs in need of these substrates. In the present overview the following issues will be briefly discussed: (i) transport and storage of fatty acids in the mammalian body, (ii) biosynthesis of albumin in the liver, (iii) localization and concentration of albumin in body fluids, (iv) interactions between albumin and fatty acids, (v) albumin structure and fatty acid binding sites, (vi) uptake of fatty acids by organs and roles for plasma albumin and (vii) lessons from patients and experimental animals lacking plasma albumin.

The influence of feeding linoleic, gamma-linolenic and docosahexaenoic acid rich oils on rat brain tumor fatty acids composition and fatty acid binding protein 7 mRNA expression

Abstract: Background Experimental studies indicate that gamma linolenic acid (GLA) and docosahexaenoic acid (DHA) may inhibit glioma cells growth but effects of oral consumption of these fatty acids on brain tumor fatty acid composition have not been determined in vivo.

Insulin acutely upregulates protein expression of the fatty acid transporter CD36 in human skeletal muscle in vivo.

Abstract: Enhanced fatty acid uptake may lead to the accumulation of lipid intermediates. This is related to insulin resistance and type 2 diabetes mellitus. Rodent studies suggest that fatty acid transporters are acutely regulated by insulin. We investigated differences in fatty acid transporter content before and at the end of a hyperinsulinemic euglycemic clamp in skeletal muscle (m. vastus lateralis) of obese, glucose-intolerant men (IGT) and obese normal glucose tolerant controls (NGT). The fatty acid transporter FAT/CD36 protein content increased 1.5-fold (P < 0.05) after 3-hrs of insulin stimulation with no difference between IGT and control subjects. No change was seen in cytosolic fatty acid binding protein (FABPc) protein content. The increase in FAT/CD36 protein content was positively related to insulin resistance as measured during the clamp (r = 0.56, P < 0.05). An increase in FAT/CD36 protein content in skeletal muscle may result in a higher fractional extraction of fatty acids (larger relative uptake) after a meal, enhancing triglyceride accumulation in the muscle. We conclude that also in obese humans the FAT/CD36 protein content in skeletal muscle is dynamically regulated by insulin in vivo on the short term.

Insulin acutely upregulates protein expression of the fatty acid transporter CD36 in human skeletal muscle in vivo

Abstract: Enhanced fatty acid uptake may lead to the accumulation of lipid intermediates. This is related to insulin resistance and type 2 diabetes mellitus. Rodent studies suggest that fatty acid transporters are acutely regulated by insulin. We investigated differences in fatty acid transporter content before and at the end of a hyperinsulinemic euglycemic clamp in skeletal muscle (m. vastus lateralis) of obese, glucose-intolerant men (IGT) and obese normal glucose tolerant controls (NGT). The fatty acid transporter FAT/CD36 protein content increased 1.5-fold (P <0.05) after 3-hrs of insulin stimulation with no difference between IGT and control subjects. No change was seen in cytosolic fatty acid binding protein (FABPc) protein content. The increase in FAT/CD36 protein content was positively related to insulin resistance as measured during the clamp (r = 0.56, P <0.05). An increase in FAT/CD36 protein content in skeletal muscle may result in a higher fractional extraction of fatty acids (larger relative uptake) after a meal, enhancing triglyceride accumulation in the muscle. We conclude that also in obese humans the FAT/CD36 protein content in skeletal muscle is dynamically regulated by insulin in vivo on the short term.

The role of membrane fatty-acid transporters in regulating skeletal muscle substrate use during exercise

Abstract: While endogenous carbohydrates form the main substrate source during high-intensity exercise, long-chain fatty acids (LCFA) represent the main substrate source during more prolonged low- to moderate-intensity exercise. Adipose tissue lipolysis is responsible for the supply of LCFA to the contracting muscle. Once taken up by skeletal muscle tissue, LCFA can either serve as a substrate for oxidative phosphorylation or can be directed towards esterification into triacylglycerol. Myocellular uptake of LCFA comprises a complex and incompletely understood process. Although LCFA can enter the cell via passive diffusion, more recent reports indicate that LCFA uptake is tightly regulated by plasma membrane-located transport proteins (fatty acid translocase [FAT/CD36], plasmalemmal-located fatty acid binding protein [FABPpm] and fatty acid transport protein [FATP]). Depending on cardiac and skeletal muscle energy demands, some of these LCFA transporters can translocate rapidly from intracellular pools to the plasma membrane to allow greater LCFA uptake. This translocation process can be induced by insulin and/or muscle contraction. However, the precise signalling pathways responsible for activating the translocation machinery remain to be elucidated. This article will provide an overview on the effects of diet, acute exercise and exercise training on the expression and/or translocation of the various LCFA transporters in skeletal muscle tissue (FAT/CD36, FABPpm, FATP).

Fatty acid-binding protein regulates LPS-induced TNF-α production in mast cells

Abstract: There has been increasing evidence for the involvement of fatty acid-binding proteins (FABPs) in the cytokine production of macrophages and dendritic cells probably through the control of cellular lipid metabolism and signal transduction Since mast cells (MCs) are recently shown to be involved in immune response through modification of cytokine production, it is possible that some FABPs could also be involved in the immune response of MCs In this study, we found that epidermal-type FABP (E-FABP) was expressed in murine bone marrow-derived MCs (BMMCs) Using BMMCs from genetically E-FABP-null mutated mice, we demonstrated that E-FABP in BMMCs plays a key role in the production of TNF-α following lipopolysaccharide (LPS) stimulation In the in vivo septic peritonitis model (cecal ligation and puncture model), E-FABP-null mice showed a significantly increased mortality compared to wild-type mice However, no significant difference in antigen-induced cytokine production was observed between wild-type and E-FABP-null BMMCs, and systemic anaphylaxis was equally induced in vivo in both wild-type and E-FABP-null mice These results suggest that E-FABP is specifically involved in the LPS-induced cytokine production of MCs, and could play a role in the host-defense against bacterial infection, possibly through regulation of TNF-α production

Peripartal feeding strategy with different n-6:n-3 ratios in sows: effect on gene expression in backfat white adipose tissue postpartum.

Abstract: The aim of this study was to describe the effects of two diets differing in n-6:n-3 ratio and prepartal feeding regime on gene expression of PPAR gamma 1a/1b, PPAR gamma 1c/1d, PPAR gamma 2, PPAR gamma coactivator 1A (PPARGC1A), GLUT4, TNF alpha, adiponectin, leptin, leptin receptor (LEPR), fatty acid binding protein 4 (FABP4), lipoprotein lipase (LPL) in sows' white adipose tissue on the first day of lactation. The relationship between mRNA expression of these genes and circulating insulin, leptin and thyroid hormones was also considered. Diets contained a low (supplemented with fish oil, f group) or a high (supplemented with sunflower oil; s group) n-6:n-3 ratio and were provided from 8 (f8, s8) or 3d (f3, s3) before parturition (onset day 8 or 3). A low n-6:n-3 ratio reduced the 1 d postpartum expression of PPAR gamma 2 and PPARGC1A but only when applied from 3 d before parturition. Circulating leptin was negatively correlated with mRNA expression of adiponectin, LEPR and LPL, whereas thyroxine was positively correlated with levels of PPARGC1A. In conclusion, the effect of dietary treatments, e.g. altering the n-6:n-3 ratio, around parturition on the expression of crucial genes in nutrient metabolism can be modulated by the duration of application before parturition.