Liver-type Fatty Acid-binding Protein Gene Research Articles

Predictive value of novel biomarkers for chronic kidney disease among workers occupationally exposed to silica.

There is a pressing need to find reliable biomarkers for the early diagnosis of silica-induced nephropathy. Abundant genes are upregulated in damaged kidneys with subsequent protein products appearing in the urine. Liver-type fatty acid-binding protein (L-FABP) and kidney injury molecule-1 (KIM-1) are among the most promising. Our objective was to study the importance of L-FABP and KIM-1 genes and their urinary proteins in the early detection of silica-induced renal injury, as compared with other conventional biomarkers. A cross-sectional study was conducted among 90 pottery workers occupationally exposed to silica, as compared to 90 controls. A full history taking and complete clinical examination were performed. Levels of serum creatinine, liver enzymes, urinary silicon, KIM-1, and L-FABP gene expression and protein products were measured. Estimated glomerular filtration rate (eGFR) was calculated, and abdominal ultrasound was performed. The results showed that the silica-exposed group had a statistically significant increase in serum creatinine and urinary silica, as well as a significant decrease in eGFR. Additionally, a significant increase in KIM-1 and L-FABP gene expression, associated with a significant increase in their urinary protein, was found among the exposed group. A positive correlation between urinary silica level and L-FABP gene expression was also found. A receiver operating characteristic curve analysis for L-FABP and KIM-1 gene as predictors for silica-induced nephropathy showed that L-FABP gene and protein specificity were greater than the KIM-1 gene and protein. Taken together, these findings suggest that the L-FABP gene and its protein product may be used as early indicators for renal injury among silica exposed workers.

Clinical evaluation of urinary liver-type fatty acid-binding protein for the diagnosis of renal diseases in dogs.

Liver-type fatty acid-binding protein (L-FABP) is a biomarker for the early detection of renal diseases in humans. L-FABP is a cytotoxic oxidation product secreted from the proximal tubules under ischemic and oxidative stress conditions. First, L-FABP gene expression in the kidney and liver was evaluated. Next, the urinary L-FABP concentrations in dogs with or without renal diseases were measured using a novel enzyme-linked immunosorbent assay kit. Urinary L-FABP was normalized relative to urinary creatinine (uCre) concentrations (µg/g uCre). Finally, the relationships between urinary L-FABP and renal biomarkers used in canine medicine or serum alanine transaminase (ALT) as an indicator of liver damage were examined. Serum and urine samples from 94 client-owned dogs including 23 dogs with renal diseases and 71 dogs without renal diseases were used for analysis. Relative L-FABP gene expression was confirmed both in the liver and kidney. Dogs with renal diseases had a significantly higher urinary L-FABP than those without, and its predictive cutoff value was 26 µg/g uCre. Urinary L-FABP was significantly correlated with serum creatinine (r=0.4674, P<0.01), urea nitrogen (r=0.4907, P<0.01), urine specific gravity (r=−0.5100, P<0.01), and urine protein/creatinine ratio (r=0.7216, P<0.01), but not with serum ALT. Hence, dogs with a high urinary L-FABP value were more likely to have renal diseases.

Liver-type fatty acid-binding protein as an early biomarker of nephropathy in type-2 diabetes

Objective The aim of this study was to evaluate serum liver-type fatty acid-binding protein (L-FABP) level as an early biomarker of diabetic nephropathy (DN) in type-2 diabetic patients. Background Tubular hypoxia upregulates the expression of the L-FABP gene in the kidney and increases the urinary excretion of L-FABP from the proximal tubules. Thus, in early stage DN, it is possible that chronic hypoxia could have induced an increase in urinary excretion of L-FABP. Patients and methods This was a case–control study that included ninety patients with type-2 diabetes mellitus selected from Military Hospital and Menoufia University Hospital who were divided into three groups: the first group comprised diabetic patients with microalbuminuria, second group comprised diabetic patients with macroalbuminuria, and the third group comprised nondiabetic patients with chronic kidney disease. A fourth group of healthy participants served as the control group. Results We found a significant increase of urinary L-FABP level in microalbuminuric diabetic patients and a significant positive correlation between urinary L-FABP level and the duration of diabetes. By using receiver operating characteristics curve analysis, calcium level at a cutoff point (≤8.3) discriminated patients with microalbuminuria from patients with macroalbuminuria, with excellent accuracy, sensitivity of 95% and specificity of 96%. Conclusion We conclude that the L-FABP level could be a suitable biomarker for early detection with good value to detect DN in patients with type-2 diabetes.

Polymorphism of L-FABP (SNP g. 1593 C&gt;T) Gene and Its Association with Fatty Acid Composition, Carcass, and Meat Quality in Cihateup Duck

Fatty acid composition, carcass, and meat quality are quantitative traits which are controlled by several genes or polygenic. One of the genes that plays important role in the fatty acid in meat quality and fatty acid composition is liver-type fatty acid-binding protein (L-FABP). The aims of this study were to identify single nucleotide polymorphism (SNP) of liver-fatty acid binding protein (L-FABP) gene and its association with fatty acid, carcass, and meat quality traits in cihateup duck. Cihateup ducks were originated from Tasikmalaya, West Java, Indonesia. The study used a total of 98 ducks aged of 12 weeks old with the average body size of 1.4±0.12 kg for PCR-RFLP analyses and 76 ducks for the association analyses. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used to identify SNP g. 1593 (C>T) of L-FABP gene. The associations of L-FABP genotypes with fatty acid, carcass, and meat quality traits were performed using T-test procedures. The result showed that the SNP of L-FABP gene was polymorphic with three genotypes (CC, CT, and TT). The Chi-square test revealed that the locus of L-FABP (g. 1593 C>T) was in Hardy - Weinberg equilibrium. L-FABP gene was significantly associated (p T) of L-FABP gene may be a useful marker for selecting and producing duck meat having desirable fatty acids and carcass and meat quality.

Molecular characterization, tissue expression, and polymorphism analysis of liver-type fatty acid binding protein in Landes geese.

Liver weight is an important economic trait in the fatty goose liver industry. Liver-type fatty acid binding protein (L-FABP) is involved in the formation and metabolism of fatty acids. Thus, we hypothesized that sequence polymorphisms in L-FABP were associated with fatty liver weight in goose. We first isolated, sequenced, and characterized the goose L-FABP gene, which had not been previously reported. The goose L-FABP gene was 2490 bp and included 4 exons coding for a 126-amino acid protein. Analysis of expression levels of the goose L-FABP gene in different tissues showed that the expression level in the liver tissue was higher than in other tissues, and was significantly higher in the liver tissue of overfed geese than in control geese. Moreover, a single nucleotide polymorphism located at 774 bp in the gene was identified in a Landes goose population. To test whether this single nucleotide polymorphism was associated with fatty liver production, liver weight and the ratio of liver to carcass weights were determined for the 3 genotypes with this single nucleotide polymorphism (TT, TG, GG) in overfed Landes geese. Our data indicate that individuals with the GG genotype had higher values for the variables measured than those with the other 2 genotypes, suggesting that L-FABP can be a selection marker for the trait of fatty liver production in goose.

Roles of human liver type fatty acid binding protein in kidney disease clarified using hL‐FABP chromosomal transgenic mice

Kidney disease develops to renal failure over a period of days, months or years, hence, clinical markers that indicate the real-time renal pathophysiological conditions is important. Liver type fatty acid binding protein (L-FABP) is a 14 kDa molecule predominantly expressed in human proximal tubules. Clinical studies demonstrate that urinary excretion of L-FABP derived from the proximal tubules is an excellent biomarker for predicting and monitoring deterioration of renal function or for early detection of kidney disease. However, in order to clarify the pathophysiological roles or dynamics of renal L-FABP in diseased settings, in vivo experimental studies of kidney diseases are indispensable. Since L-FABP is not endogenously expressed in murine kidneys, a transgenic (Tg) mouse model with expression of the human L-FABP gene was established. This review article summarizes the findings on the pathophysiological roles and dynamics of renal human L-FABP in the recent experimental studies performed using this Tg mouse model.

A novel SNP of liver-type fatty acid-binding protein gene in duck and its associations with the intramuscular fat

Liver-type fatty acid-binding protein (L-FABP) is a member of intracellular lipid-binding proteins involved in the transportation of fatty acids. We detected the polymorphisms of duck L-FABP gene and its association with the intramuscular fat (IMF) and other fat-related traits. The complete sequence of duck L-FABP gene (four exons and three introns, 2,542 bp) was obtained in this study. The polymorphism of L-FABP gene was examined with direct DNA sequencing method in 231 individuals from different breeds, and a novel single nucleotide polymorphism in the exon 3 was detected. The polymorphism was shown to be associated with the contents of C16:0, C18:3 and the total IMF in pectoral muscle. The content of C16:0 in genotype CC was significantly higher than CT (P < 0.01) and TT (P < 0.01), and the genotype CT was higher than TT (P < 0.01). The content of C18:3 in genotype TT was significantly higher than CC and CT (P < 0.01), whereas the genotype CC and CT had no significant difference (P > 0.05). The content of IMF in genotype CC was significantly higher than CT (P < 0.01). However, no significant difference was detected between genotype CC and TT or genotype CT and TT (P > 0.05).

Effects of dietary lipids and Clostridium butyricum on serum lipids and lipid-related gene expression in broiler chickens

The effect of dietary lipids and Clostridium butyricum supplementation on circulating lipids and the transcription of selected genes involved in lipid metabolism were investigated in broiler chickens. One hundred and sixty-day-old broilers (Arbor Acres) were divided into four treatment groups in a 2 × 2 factorial arrangement and fed four diets with two lipid sources (soybean oil or fish oil) and two levels of C. butyricum (0 or 5 g/kg) for a period of 6 weeks. Serum concentrations of total cholesterol and low-density lipoprotein cholesterol were lower (P < 0.05) in broilers fed diets containing fish oil than in those fed diets containing soybean oil. Fish oil significantly reduced (P < 0.05) hepatic fatty acid synthase and lipoprotein lipase (LPL) activities in abdominal fat. In contrast, fish oil significantly increased (P < 0.05) breast muscle LPL activity and hepatic peroxisome proliferator-activated receptor-α and LPL gene expression. The addition of C. butyricum significantly increased (P < 0.05) LPL activity in abdominal fat and liver-type fatty acid-binding protein gene expression in jejunal mucosa. The results of this study indicated that the reduced abdominal fat in broilers fed fish oil as observed may be due to augmented hepatic fatty acid catabolism and lower hepatic fat synthesis. The increased intramuscular fat content in breast muscle of broilers fed C. butyricum as described may be the result of enhanced fatty acid uptake.

Possible Role of Fatty Acids in Milk as the Regulator of the Expression of Cytosolic Binding Proteins for Fatty Acids and Vitamin A through PPAR.ALPHA. in Developing Rats

Fatty acids in milk are thought to play an important role in intestinal maturation and gene expression in the postnatal small intestine. In this study, we determined the jejunal mRNA levels, in rats, of peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARdelta which are nuclear receptors for fatty acids. We also measured expression of their target genes during the postnatal period, namely liver type fatty acid-binding protein (L-FABP) and cellular retinol-binding protein, type II (CRBPII). The mRNA levels of PPARalpha, L-FABP and CRBPII, but not PPARdelta, gradually increased during the suckling period and then sharply declined to a low level at the end of the weaning period. Rat pups at 17 d of age, weaned to a high-fat diet, showed significantly greater mRNA levels of PPARalpha, L-FABP and CRBPII than those weaned to a low-fat diet. Oral administration of PPARalpha ligand, WY14,643 during four consecutive days of the weanling period caused a parallel increase in the mRNA levels of PPARalpha, L-FABP and CRBPII genes. Furthermore, caprylic acid and oleic acid, which are major components of fatty acids in milk, induced jejunal PPARalpha, L-FABP and CRBPII gene expression. Our results suggest that fatty acids in milk may play a pivotal role in maintaining an enhanced level of expression of L-FABP and CRBPII genes in the small intestine, presumably by acting as inducers of PPARalpha gene expression.

Liver-Type Fatty Acid-Binding Protein Attenuates Renal Injury Induced by Unilateral Ureteral Obstruction

Liver-type fatty-acid-binding protein (L-FABP), which has high affinity for long-chain fatty acid oxidation products, may be an effective endogenous antioxidant. To examine the role of L-FABP in tubulointerstitial damage, we used a unilateral ureteral obstruction (UUO) model. We established human L-FABP (hL-FABP) gene transgenic (Tg) mice and compared the tubulointerstitial pathology of the Tg mice (n = 23) with that of the wild-type (WT) mice (n = 23). Mice were sacrificed on days 2, 4, 5, or 7 after UUO. Although mouse L-FABP was not expressed in WT mice, hL-FABP was expressed in the proximal tubules of the Tg mice with UUO (UUO-Tg) and in sham-operated Tg mice. The expression of renal hL-FABP was significantly increased in UUO-Tg compared with sham-operated Tg mice. The number of macrophages (F4/80) infiltrating the interstitium and the level of expression of MCP-1 and MCP-3 were significantly lower in UUO-Tg kidneys compared with UUO-WT kidneys. In UUO-Tg kidneys, the degree of the tubulointerstitial injury and the deposition of type I collagen were significantly lower than that of UUO-WT kidneys. On day 7, lipid peroxidation product accumulated in the UUO-WT kidneys but not in that of UUO-Tg kidneys. In conclusion, renal L-FABP may reduce the oxidative stress in the UUO model, ameliorating tubulointerstitial damage.

In vivo studies of liver-type fatty acid binding protein (L-FABP) gene expression in liver of transgenic zebrafish (Danio rerio)

Mammalian liver fatty acid binding protein (L-FABP) is a small cytosolic protein in various tissues including liver, small intestine and kidney and is thought to play a crucial role in intracellular fatty acid trafficking and metabolism. To better understand its tissue-specific regulation during zebrafish hepatogenesis, we isolated 5′-flanking sequences of the zebrafish L-FABP gene and used a green fluorescent protein (GFP) transgenic strategy to generate liver-specific transgenic zebrafish. The 2.8-kb 5′-flanking sequence of zebrafish L-FABP gene was sufficient to direct GFP expression in liver primordia, first observed in 2 dpf embryos and then continuously to the adult stage. This pattern of transgenic expression is consistent with the expression pattern of the endogenous gene. F2 inheritance rates of 42–51% in all the seven transgenic lines were consistent with the ratio of Mendelian segregation. Further, hhex and zXbp-1 morphants displayed a visible liver defect, which suggests that it is possible to establish an in vivo system for screening genes required for liver development.

CDNA sequence and tissue-specific expression of a basic liver-type fatty acid binding protein in adult zebrafish ( Danio rerio)

We have determined the nucleotide sequence for a cDNA clone derived from zebrafish ( Danio rerio) that codes for a fatty acid binding protein (FABP). Amino acid sequence similarity of the zebrafish FABP was highest to FABPs isolated from the livers of catfish, chicken, salamander and iguana. The open-reading frame of the zebrafish FABP cDNA codes for a protein of 14.0 kDa with a calculated isoelectric point of 8.8. The zebrafish liver-type FABP (L-FABP) cDNA hybridized to single restriction fragments of total zebrafish genomic DNA digested with the restriction endonucleases HaeIII or EcoRI suggesting that a single copy of the L-FABP gene is present in the zebrafish genome. Northern blot analysis demonstrated that the zebrafish L-FABP cDNA hybridized to a transcript of 700 nucleotides in total zebrafish RNA. In situ hybridization and emulsion autoradiography revealed that the L-FABP was expressed exclusively in the liver of the adult zebrafish. Based on amino acid sequence similarity, the isoelectric point and its tissue-specific pattern of expression, we conclude that this zebrafish FABP belongs to the basic liver-type FABPs only found, thus far, in non-mammalian vertebrates.