Fatty Acid Binding Protein 4 Gene Research Articles

Abstract 15785: Effects of Empagliflozin on Fatty Acid Binding Protein 4 and Body Composition in Patients Without Diabetes but With Risk Factors for Adverse Cardiac Remodeling From the Empa-Heart 2 Cardiolink-7 Randomized Clinical Trial

Background: Prevention of the progression from stage B to C heart failure is an unmet need. Increased fat composition in skeletal muscle is one of the mechanisms associated with heart failure with preserved ejection fraction. Fatty acid binding protein 4 (FABP4) is known to facilitate the transport of fatty acid to tissue mitochondria for lipid oxidation. Knockdown of FABP4 gene is associated with increased body weight and fat mass in animal models. We sought to determine if Sodium-glucose co-transporter 2 (SGLT2) inhibition with empagliflozin leads to change in blood FABP4 levels and improvement in body composition in patients without diabetes and significant heart failure but with risk factors for adverse cardiac remodeling. Hypothesis: Empagliflozin increases blood FABP4 concentration and lowers body fat composition without changes in skeletal muscle mass. Methods: A total of 42 individuals between 40 and 80 years of age without diabetes but with risk factors for adverse cardiac remodeling were randomized to empagliflozin (10 mg/day; n=21) and placebo (n=21) groups for 6 months. Body composition parameters measured by bio-impedance analysis (InBody-720) included body weight (BW), skeletal muscle mass (SMM) and body fat mass (BFM) at baseline and 6 months follow up. Blood FABP4 concentrations were measured at the same time points. Results: There were no significant differences between two groups in baseline characteristics, BW, SMM, BFM, or FABP4. From baseline to 6 months, empagliflozin compared to placebo significantly increased blood FABP4 concentrations (6067.3 ± 7591.4 pg/ml vs 2714.9 ± 11232.6 pg/ml, p = 0.002), but decreased BW (-1.19 ± 1.01 kg vs 0.34 ± 2.59 kg, p = 0.018) and BFM (-0.68 ± 1.27 kg vs 0.53 ± 2.01 kg, p = 0.024). However, empagliflozin did not significantly affect changes in SMM from baseline to 6 months (-4.01 ± 0.70 kg vs -0.17 ± 0.96 kg, p = 0.387). Conclusions: SGLT2 inhibition with empagliflozin, in patients with neither diabetes nor significant heart failure but with risk factors for adverse cardiac remodeling, increased blood FABP4 concentrations and ameliorated BW and body fat composition with no effect on skeletal muscle mass following 6 months of treatment.

Association of fatty acid binding protein-4 (FABP-4) T87C and rs8192688 gene polymorphisms and FABP-4 level with cardiovascular disease susceptibility in type 2 diabetic patients

Type 2 Diabetes Mellitus (T2DM) is known to cause dyslipidemia and increase the risk of cardiovascular disease (CVD). Fatty acid binding protein (FABP)-4 plays a significant role in various stages of T2DM and CVD. Although it has been demonstrated that genetic variations of the FABP-4 gene can affect insulin sensitivity, the results obtained so far are controversial. The aim of this study was to investigate the possible association between T87C and rs8192688 polymorphisms and serum levels of FABP-4 with CVD susceptibility in T2DM patients. The study included 70 healthy controls, 70 individuals with T2DM, and 70 T2DM patients with CVD. Genomic DNA was extracted, and FABP-4 T87C and rs8192688 gene polymorphic sites were amplified using the ARMS-PCR method. Lipid profile and FABP-4 serum levels were significantly higher in T2DM patients with CVD compared to those with only T2DM (p < 0.05). Additionally, FABP-4 T87C gene polymorphism (TC genotypes) and dominant model (TT vs. TC + CC) were significantly associated with a decreased risk of both T2DM and T2DM with CVD patients (p < 0.05). Patients carrying TC + CC genotypes had significantly lower levels of triglyceride and FABP-4 compared to those carrying the TT genotype (p < 0.05). There was no significant association between FABP-4 rs8192688 polymorphism and either T2DM or CVD disease. It appears that FABP-4 T87C polymorphism decreases FABP-4 levels leading to decreased serum TG levels. Since both T2DM and CVD have inflammatory backgrounds, reducing inflammation can improve insulin sensitivity and lower TG levels in these patients.

Effects of dietary supplementation with algae, sunflower oil, or soybean oil, and age on fat content, fatty acid profile and the expression of related genes in rabbits

&gt;Abstract The aim of this study was determine the effect of different dietary supplements (algae, sunflower oil, or soybean oil) and age (12 and 18 weeks) on the fat content, fatty acid (FA) profile, and expression of the fat mass and obesity associated (FTO) and fatty acid binding protein 4 (FABP4) genes in rabbit muscle. Rabbits (n = 160) were randomly divided into four groups. The control group (C) received non-supplemented pellets, while in the other groups the pellet contained 1% algae (A), 3% sunflower oil (OS), or 3% soybean (SO) oil. Soybean and sunflower oil (3%) in the diet increased the linoleic acid (LA) content in meat of 12-week-old rabbits. The use of algae (1%) in the diet increased the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared with the vegetable oil and control groups, and decreased the n-6/n-3 ratio. The effect of the diet on FTO and FABP4 gene expression depended on the age of the rabbits. In older animals (18 weeks of age) the expression of these genes was highest in the group with 1% algae. Furthermore, the FA profile and FTO and FABP4 gene expression were affected by the age of rabbits, but not by sex. The results showed that diet is an important tool to modulate the FA profile in rabbit meat by changing the expression of fat metabolism–related genes.

A Novel Missense SNP in the Fatty Acid-Binding Protein 4 (FABP4) Gene is Associated with Growth Traits in Karakul and Awassi Sheep.

The fatty acid-binding protein 4 (FABP4) plays a crucial role in the transportation and metabolism of fatty acids. It binds to long-chain fatty acids and facilitates their transport within cells. FABP4 is involved in lipid metabolism, insulin sensitivity, inflammation, and energy homeostasis. This study was conducted to assess the association between the FABP4 gene and growth traits in Karakul and Awassi sheep. A PCR-single strand conformation polymorphism (SSCP) protocol was utilized to assess the polymorphism of FABP4 PCR products with growth traits measured at birth, three, six, nine, and twelve-month intervals. One non-synonymous SNP was identified in the second exon, in which threonine was converted to aspartate in the 61st position in FABP4 (p.61Thr > Asp). This novel SNP showed significant associations with all growth traits measured at all age intervals. The results showed that lambs with the TT genotype exhibited higher growth traits than those with the GT and GG genotypes, respectively. The conducted prediction showed a clearly deleterious effect of p.61Thr > Asp on FABP4 structure, which was accompanied by reduced fatty acid binding efficiency. Owing to the predicted damaging effects caused by p.61Thr > Asp on FABP, lower levels of lipid transport and its consequent increased weight gain and other growth trait indices are expected. Therefore, a putative mechanism through which lambs with these genotypes exhibit higher growth traits is proposed. The FABP4 gene is suggested as apromising markerto improve growth traits in Karakul and Awassi sheep. However, more research is required to validate this mechanism.

Adipose tissue-derived FABP4 mediates glucagon-stimulated hepatic glucose production in gestational diabetes.

One of the most common complications of pregnancy is gestational diabetes mellitus (GDM), which may result in significant health threats of the mother, fetus and the newborn. Fatty acid-binding protein 4 (FABP4) is an adipokine that regulates glucose homeostasis by promoting glucose production and liver insulin resistance in mouse models. FABP4 levels are increased in GDM and correlates with maternal indices of insulin resistance, with a rapid decline post-partum. We therefore aimed to determine the tissue origin of elevated circulating FABP4 levels in GDM and to assess its potential contribution in promoting glucagon-induced hepatic glucose production. FABP4 protein and gene expression was determined in biopsies from placenta, subcutaneous (sWAT) and visceral (vWAT) white adipose tissues from GDM and normoglycaemic pregnant women. FABP4 differential contribution in glucagon-stimulated hepatic glucose production was tested in conditioned media before and after its immune clearance. We showed that FABP4 is expressed in placenta, sWAT and vWAT of pregnant women at term, with a significant increase in its secretion from vWAT of women with GDM compared with normoglycaemic pregnant women. Neutralizing FABP4 from both normoglycaemic pregnant women and GDM vWAT secretome, resulted in a decrease in glucagon-stimulated hepatic glucose production. This study provides new insights into the role of adipose tissue-derived FABP4 in GDM, highlighting this adipokine, as a potential co-activator of glucagon-stimulated hepatic glucose production during pregnancy.

Detection of SNPs in FABP4 Gene and Its Relationship with Milk Quality Traits in Iraqi Jenoubi Cows

Jenoubi cattle breed classified as a Bos indicus L., is one of Iraqi indigenous cattle that kept for milk production purpose, but the influence of fatty acid-binding protein 4 (FABP4) on milk-related traits remain poorly understood. The current study was conducted to investigate the effect of single nucleotide polymorphisms (SNPs) in the FABP4 gene of Jenoubi cows. The DNA samples were extracted from the blood of 21 cows. Along 565-bp nucleotide (nt) amplicon from the intron 2- exon 3- intron 3 of FABP4 was amplified by polymerase chain reaction (PCR) while forward sequencing was used to detect SNPs and results were analyzed using bioinformatics software. The findings resulted the existence of two SNPs (c.3689G&gt;A and c.3709G&gt;C) in the exon 3 and four SNPs (g.3494A&gt;C, g.3531A&gt;T, g.3743T&gt;C and g.3765T&gt;C) in the intron regions. Therefore, three haplotypes of FABP4 gene were obtained in this study based on three SNPs of g.3494A&gt;C, g.3531A&gt;T and g.3765T&gt;C. Nonetheless, those haplotypes were not significantly influencing to the milk quality traits of Jenoubi cows. However, the SNPs examined in this study might not be used as potential DNA marker to improve milk production traits of the current breed.

ҚАЗАҚТЫҢ ҚҰЙРЫҚТЫ ҚОЙ ТҰҚЫМЫНЫҢ ӨНІМДІЛІК БЕЛГІЛЕРІМЕН БАЙЛАНЫСҚАН КАНДИДАТ-ГЕНДЕРДІҢ АЛЛЕЛЬДІК ПОЛИМОРФИЗМІ

In recent years, research aimed at developing breeding methods based on the use of DNA markers associated with the level of productivity has become particularly important. The introduction of this technology into the domestic production of mutton is on urgent task of great practical importance for the development of this industry. In this regard, the goal was set to study the polymorphism of the alleles of growth hormone (GH2), insulin-like growth factor (IGF1), myostatin (MSTN), and fatty acid binding protein-4 (FABP4) genes associated with the productivity of Kazakh fat-tailed sheep. Blood samples were used to study animal DNA. The analysis of polymorphism in genes was carried out with the help of test systems that were specially designed to carry out research work in the laboratory of Molecular Bases of Breeding of the All-Russian institute of Animal Husbandry named after L.K. Ernst (Russia). During the study of polymorphic sistems of blood proteins, the degree of differentiation of the genetic structures of the Kazakh fat-tailed breed by alleles and genotypes of polymorphic proteins was determined. As a result of testing, it was revealed that in the population of Kazakh fat-tailed sheep, the GH2 and IGF1 genes are polymorphic and the MSTN and FABP4 genes are monomorphic. Identification of candidate genes associated with signs of meat productivity of the Kazakh fat-tailed breed can be used to develop marker breeding programs, the use of which in practice can significantly improve the efficiency of breeding work.

Lipogenic Gene Single Nucleotide Polymorphic DNA Markers Associated with Intramuscular Fat, Fat Melting Point, and Health-Beneficial Omega-3 Long-Chain Polyunsaturated Fatty Acids in Australian Pasture-Based Bowen Genetics Forest Pastoral Angus, Hereford, and Wagyu Beef Cattle.

This study used targeted sequencing aimed at identifying single nucleotide polymorphisms (SNP) in lipogenic genes and their associations with health-beneficial omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA), intramuscular fat (IMF), and fat melting point (FMP) of the M. longissimus dorsi muscle in Australian pasture-based Bowen Genetics Forest Pastoral Angus, Hereford, and Wagyu cattle. It was hypothesized that SNP encoding for the fatty acid-binding protein 4 (FABP4), stearoyl-CoA desaturase (SCD), and fatty acid synthase (FASN) genes will be significantly associated with health-beneficial n-3 LC-PUFA and the meat eating quality traits of IMF and FMP in an Australian pasture-based beef production system. Two SNP mutations, g.21267406 T>C and g.21271264 C>A, in the SCD gene were significantly (p < 0.05) associated with IMF, FMP, oleic acid (18:1n-9), linoleic acid (LA) 18:2n-6, alpha-linolenic acid (ALA) 18:3n-3, eicosapentaenoic acid (EPA) 20:5n-3, docosahexaenoic acid (DHA) 22:6-n-3, and docosapentaenoic acid (DPA) 22:5n-3. Significant positive correlations (p < 0.05) between FASN SNP g. 50787138 A>G and FMP, 18:1n-9, ALA, EPA, DHA, DPA, and total n-3 LC-PUFA were also detected. An SNP (g.44678794 G>A) in the FABP4 gene was associated with FMP. These results provide significant insights into the contributions of lipogenic genes to intramuscular fat deposition and the biosynthesis of health-beneficial n-3 LC-PUFA. The findings also unravel the potential use of lipogenic gene polymorphisms in marker-assisted selection to improve the content of health-promoting n-3 LC-PUFA and meat eating quality traits in Australian pasture-based Bowen Genetics Forest Pastoral Angus, Hereford, and Wagyu beef cattle.

Single Nucleotide Polymorphisms in the Fatty Acid Binding Protein 4, Fatty Acid Synthase and Stearoyl-CoA Desaturase Genes Influence Carcass Characteristics of Tropical Crossbred Beef Steers

This study explored the identification of single nucleotide polymorphisms (SNP) in fatty acid binding protein 4 (FABP4), stearoyl-CoA desaturase (SCD), and fatty acid synthase (FASN) genes that may influence the carcass traits of tropical crossbred beef cattle. The hypothesis tested was that SNP in the FABP4, SCD, and FASN genes are associated with chiller-assessed carcass traits of tropically adapted northern Australian crossbred beef cattle. Fifty Bos indicus and Bos taurus crossbred steers were backgrounded on either buffel grass only, or buffel grass and desmanthus mixed pastures for 147 days and finished in a commercial feedlot for 110 days. Steers were slaughtered within 48 h of leaving the feedlot within a lairage period not exceeding 12 h and carcasses graded 12 h after slaughter. Next-generation sequencing of the FASN, FABP4, and SCD genes identified multiple SNP loci that were correlated and significantly associated with carcass traits. The FABP4 g.44677205A&gt;G locus was significantly associated with hump height and correlated with loin eye muscle area (EMA; p &lt; 0.05). Polymorphism in the SCD gene g.21275851C&gt;A locus was associated with subcutaneous fat depth and marbling score (p &lt; 0.05). The CC genotype had a higher subcutaneous fat depth and marbling score (p &lt; 0.05) than the AA genotype. Significant correlations were observed between carcass marbling score and subcutaneous fat depth within the FASN SNP locus (p &lt; 0.05). Therefore, the hypothesis that SNP in the FABP4, SCD, and FASN genes are associated with chiller-assessed carcass traits of tropically adapted northern Australian crossbred beef cattle was accepted. These findings suggest that SNP in the FABP4, SCD, and FASN genes may be used in carcass grading and meat quality improvement through marker-assisted selection of northern Australian crossbred beef cattle.

Towards Sustainable Sources of Omega-3 Long-Chain Polyunsaturated Fatty Acids in Northern Australian Tropical Crossbred Beef Steers through Single Nucleotide Polymorphisms in Lipogenic Genes for Meat Eating Quality

This study aimed to identify single nucleotide polymorphisms (SNP) in lipogenic genes of northern Australian tropically adapted crossbred beef cattle and to evaluate associations with healthy lipid traits of the Longissimus dorsi (loin eye) muscle. The hypothesis tested was that there are significant associations between SNP loci encoding for the fatty acid binding protein 4 (FABP4), stearoyl-CoA desaturase (SCD) and fatty acid synthase (FASN) genes and human health beneficial omega-3 long-chain polyunsaturated fatty acids (ω3 LC-PUFA) within the loin eye muscle of northern Australian crossbred beef cattle. Brahman, Charbray, and Droughtmaster crossbred steers were fed on Rhodes grass hay augmented with desmanthus, lucerne, or both, for 140 days and the loin eye muscle sampled for intramuscular fat (IMF), fat melting point (FMP), and fatty acid composition. Polymorphisms in FABP4, SCD, and FASN genes with significant effects on lipid traits were identified with next-generation sequencing. The GG genotype at the FABP4 g.44677239C&gt;G locus was associated with higher proportion of linoleic acid than the CC and CG genotypes (p &lt; 0.05). Multiple comparisons of genotypes at the SCD g.21266629G&gt;T locus indicated that the TT genotype had significantly higher eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids than GG genotype (p &lt; 0.05). Significant correlations (p &lt; 0.05) between FASN SNP and IMF, saturated and monounsaturated fatty acids were observed. These results provide insights into the contribution of lipogenic genes to intramuscular fat deposition and SNP marker-assisted selection for improvement of meat-eating quality, with emphasis on alternate and sustainable sources of ω3 LC-PUFA, in northern Australian tropical crossbred beef cattle, hence an acceptance of the tested hypothesis.

Fatty Acid-Binding Protein 4 Inhibition Promotes Locomotor and Autonomic Recovery in Rats following Spinal Cord Injury.

The inflammatory response associated with traumatic spinal cord injury (SCI) contributes to locomotor and sensory impairments. Pro-inflammatory (M1) macrophages/microglia (MϕMG) are the major cellular players in this response as they promote chronic inflammation resulting in injury expansion and tissue damage. Fatty acid-binding protein 4 (FABP4) promotes M1 MϕMG differentiation; however, it is unknown if FABP4 also plays a role in the etiology of SCI. The present study investigates whether FABP4's gene expression influences functional recovery following SCI. Analysis of quantitative polymerase chain reaction data shows a robust induction of FABP4 messenger RNA (mRNA; >100 fold) in rats subjected to a T9-T10 contusion injury compared with control. Western blot experiments reveal significant upregulation of FABP4 protein at the injury epicenter, and immunofluorescence analysis identifies that this upregulation occurs in CD11b+ MϕMG. Further, upregulation of FABP4 gene expression correlates with peroxisome proliferator-activated receptor γ (PPARγ) downregulation, inactivation of Iκβα, and the activation of the NF-κB pathway. Analysis of locomotor recovery using the Basso-Beattie-Bresnahan's locomotor scale and the CatWalk gait analysis system shows that injured rats treated with FABP4 inhibitor BMS309403 have significant improvements in locomotion compared with vehicle controls. Additionally, inhibitor-treated rats exhibit enhanced autonomic bladder reflex recovery. Immunofluorescence experiments also show the administration of the FABP4 inhibitor increases the number of CD163+ and liver arginase+ M2 MϕMG within the epicenter and penumbra of the injured spinal cord 28 days post-injury. These findings show that FABP4 may significantly exacerbate locomotor and sensory impairments during SCI by modulating macrophage/microglial activity.

Two cSNPs sites in the fatty acid-binding protein 4 (FABP4) gene and their association analysis with body measurement data in five Chinese cattle breeds

Single nucleotide polymorphisms (SNPs) include the transition and transversion of a single base. In this study, we found two cSNPs (rs110757796 and rs110652478) in the FABP4 (fatty acid-binding protein 4) gene and tested their population genetic parameters in five Chinese cattle breeds. FABP4 is a key marker molecule for lipid production. It plays a crucial role in the growth and development of animals. Thus, we also analyze the association between the two cSNPs of FABP4 gene and body measurement data of Chinese cattle. Our results were indicated that rs110757796 was significantly associated with the chest width in Chinese cattle groups (p < 0.05). In addition, we tested the spatiotemporal expression profile of the bovine FABP4 gene and effect of genetic variation on its expression. It was found that bovine FABP4 gene has tissue-differential expression. Then, the genetic variation located on the exon has a certain effect on the expression of FABP4 gene in bovine muscle. Overall, our results provide that FABP4 could as a candidate gene to improve the progress of cattle molecular breeding.

The low-expression variant of FABP4 is associated with cardiovascular disease in type 1 diabetes

Background and Aims: The adipokine fatty-acid binding protein 4 (FABP4) has been implicated in the pathogenesis of cardiometabolic disorders. Blocking the action of FABP4 through genetic or pharmacological means in a preclinical setting or analyzing the effects of genetically reduced expression in humans is suggested to protect against obesity-related metabolic derangements and atherosclerosis. As cardiovascular disease (CVD) is common in individuals with type 1 diabetes (T1D), we examined the role of FABP4 in complications of T1D, focusing on the low-expression promoter polymorphism (rs77878271,A>G) of the FABP4 gene.

The Low-Expression Variant of FABP4 Is Associated With Cardiovascular Disease in Type 1 Diabetes.

Fatty acid binding protein 4 (FABP4) is implicated in the pathogenesis of cardiometabolic disorders. Pharmacological inhibition or genetic deletion of FABP4 improves cardiometabolic health and protects against atherosclerosis in preclinical models. As cardiovascular disease (CVD) is common in type 1 diabetes, we examined the role of FABP4 in the development of complications in type 1 diabetes, focusing on a functional, low-expression variant (rs77878271) in the promoter of the FABP4 gene. For this, we assessed the risk of CVD, stroke, coronary artery disease (CAD), end-stage kidney disease, and mortality using Cox proportional hazards models for the FABP4 rs77878271 in 5,077 Finnish individuals with type 1 diabetes. The low-expression G allele of rs77878271 increased the risk of CVD, independent of confounders. Findings were tested for replication in 852 Danish and 3,678 Finnish individuals with type 1 diabetes. In the meta-analysis, each G allele increased the risk of stroke by 26% (P = 0.04), CAD by 26% (P = 0.006), and CVD by 17% (P = 0.003). In Mendelian randomization, a 1-SD unit decrease in FABP4 increased risk of CAD 2.4-fold. Hence, in contrast with the general population, among patients with type 1 diabetes the low-expression G allele of rs77878271 increased CVD risk, suggesting that genetically low FABP4 levels may be detrimental in the context of type 1 diabetes.

FABP4 and omentin-1 gene expression in epicardial adipose tissue from coronary artery disease patients.

Omentin-1 and fatty acid-binding protein 4 (FABP4) are adipose tissue adipokines linked to obesity-associated cardiovascular complications. The aim of this study was to investigate epicardial adipose tissue (EAT) omentin-1 and FABP4 gene expression in obese and non-obese patients with coronary artery disease (CAD). Omentin-1 and FABP4 mRNA levels in EAT and paired subcutaneous adipose tissue (SAT) as well as adipokine serum concentrations were assessed in 77 individuals (61 with CAD; 16 without CAD (NCAD)). EAT FABP4 mRNA level was decreased in obese CAD patients when compared to obese NCAD individuals (p=0.001). SAT FABP4 mRNA level was decreased in CAD patients compared to NCAD individuals without respect to their obesity status (p=0.001). Omentin-1 mRNA level in EAT and SAT did not differ between the CAD and NCAD groups. These findings suggest that omentin-1 gene expression in adipose tissue is not changed during CAD; downregulated FABP4 gene expression in SAT is associated with CAD while EAT FABP4 gene expression is decreased only in obesity-related CAD.

Short communication: Molecular markers for epithelial cells across gastrointestinal tissues and fecal RNA in preweaning dairy calves

The objective of this study was to compare the transcription of gene markers for gastrointestinal (GI) epithelial cells, including fatty acid binding protein 2 (FABP2) and cytokeratin 8 (KRT8), and tight junction complex genes (TJP1, CLDN1, CLDN4) in fecal RNA against several GI tract tissue sections in dairy calves. Eight healthy Jersey calves were euthanized at 5 wk of age, and postmortem samples were collected from rumen, duodenum, jejunum, ileum, large intestine, cecum, and feces for total RNA isolation. Tissues and fecal samples were immediately frozen in liquid nitrogen until RNA isolation. A real-time quantitative PCR analysis was performed using a single standard curve composited of equal amounts of all samples, including cDNA from fecal and GI tract tissues. The mRNA expression of the tight junctions TJP1, CLDN1, and CLDN4 was greater in fecal RNA compared with lower GI tract tissues (i.e., duodenum, jejunum, ileum, large intestine, and cecum). Similar to fecal RNA, rumen tissue had greater expression of tight junctions CLDN1 and CLDN4 than lower GI tract tissues. Similarly, rumen tissue had greater expression of TPJ1 than all lower GI tract tissues except duodenum. The expression of TJP1 and CLDN4 was greater in fecal RNA than in rumen tissue; in contrast, CLDN1 mRNA expression was greater in rumen tissue than in the fecal RNA. The expression of FABP2 was greater in duodenum in comparison to all tissue except ileum. The mRNA expression of FABP2 in fecal samples was similar to jejunum and ileum. The expression of KRT8 in fecal samples was similar to duodenum, large intestine, and cecum. The fecal RNA had a greater expression of KRT8 in comparison to jejunum and ileum. The rumen tissue had the lowest mRNA expression of KRT8. The expression levels of FABP2, KRT8, and tight junction genes observed in fecal transcripts suggest that a considerable amount of RNA derived from GI tract epithelial cells can be detected in fecal RNA, which is in agreement with previous data in neonatal dairy calves and other biological models including humans, rodents, and primates. The greater expression of tight junctions in fecal RNA in comparison to sections of the low GI remains to be understood, and due to the importance of tight junctions in GI physiology, further clarification of this effect is warranted. The similarities in mRNA expression of FABP2 and KRT8 between fecal RNA and intestinal sections add up to the accumulating evidence that fecal RNA can be used to investigate molecular alterations in the GI tract of neonatal dairy calves. Further research in this area should include high-throughput transcriptomic analysis via RNA-seq to uncover novel molecular markers for specific sections of the GI tract of neonates.

A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder.

Autism spectrum disorder is a neurodevelopmental disorder characterized by difficulties in social communication and interaction, as well as repetitive and characteristic patterns of behaviour. Although the pathogenesis of autism spectrum disorder is unknown, being overweight or obesity during infancy and low weight at birth are known as risks, suggesting a metabolic aspect. In this study, we investigated adipose tissue development as a pathophysiological factor of autism spectrum disorder by examining the serum levels of adipokines and other metabolic markers in autism spectrum disorder children (n = 123) and typically developing children (n = 92) at 4–12 years of age. Among multiple measures exhibiting age-dependent trajectories, the leptin levels displayed different trajectory patterns between autism spectrum disorder and typically developing children, supporting an adipose tissue-dependent mechanism of autism spectrum disorder. Of particular interest, the levels of fatty acid binding protein 4 (FABP4) were significantly lower in autism spectrum disorder children than in typically developing subjects, at preschool age (4–6 years old: n = 21 for autism spectrum disorder and n = 26 for typically developing). The receiver operating characteristic curve analysis discriminated autism spectrum disorder children from typically developing children with a sensitivity of 94.4% and a specificity of 75.0%. We re-sequenced the exons of the FABP4 gene in a Japanese cohort comprising 659 autism spectrum disorder and 1000 control samples, and identified two rare functional variants in the autism spectrum disorder group. The Trp98Stop, one of the two variants, was transmitted to the proband from his mother with a history of depression. The disruption of the Fabp4 gene in mice evoked autism spectrum disorder-like behavioural phenotypes and increased spine density on apical dendrites of pyramidal neurons, which has been observed in the postmortem brains of autism spectrum disorder subjects. The Fabp4 knockout mice had an altered fatty acid composition in the cortex. Collectively, these results suggest that an ‘adipo-brain axis’ may underlie the pathophysiology of autism spectrum disorder, with FABP4 as a potential molecule for use as a biomarker.

Genetics of Omega-3 Long-Chain Polyunsaturated Fatty Acid Metabolism and Meat Eating Quality in Tattykeel Australian White Lambs.

Meat eating quality with a healthy composition hinges on intramuscular fat (IMF), fat melting point (FMP), tenderness, juiciness, flavour and omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) content. These health-beneficial n-3 LC-PUFA play significant roles in optimal cardiovascular, retinal, maternal and childhood brain functions, and include alpha linolenic (ALA), eicosapentaenoic (EPA), docosahexaenoic (DHA) and docosapentaenoic (DPA) acids. The primary objective of this review was to access, retrieve, synthesise and critically appraise the published literature on the synthesis, metabolism and genetics of n-3 LC-PUFA and meat eating quality. Studies on IMF content, FMP and fatty acid composition were reviewed to identify knowledge gaps that can inform future research with Tattykeel Australian White (TAW) lambs. The TAW is a new sheep breed exclusive to MARGRA brand of lamb with an outstanding low fat melting point (28–39°C), high n-3 LC-PUFA EPA+DHA content (33–69mg/100g), marbling (3.4–8.2%), tenderness (20.0–38.5N) and overall consumer liking (7.9–8.5). However, correlations between n-3 LC-PUFA profile, stearoyl-CoA desaturase (SCD), fatty acid binding protein 4 (FABP4), fatty acid synthase (FASN), other lipogenic genes and meat quality traits present major knowledge gaps. The review also identified research opportunities in nutrition–genetics interactions aimed at a greater understanding of the genetics of n-3 LC-PUFA, feedlot finishing performance, carcass traits and eating quality in the TAW sheep. It was concluded that studies on IMF, FMP and n-3 LC-PUFA profiles in parental and progeny generations of TAW sheep will be foundational for the genetic selection of healthy lamb eating qualities and provide useful insights into their correlations with SCD, FASN and FABP4 genes.

Single-nucleotide polymorphisms in FABP4 gene associated with growth traits in Egyptian sheep.

Aim:The present study was performed to assess the association of single-nucleotide polymorphisms (SNPs) in the fatty acid-binding protein 4 (FABP4) gene with birth weight (BW), final weight (FW), and average daily gain (ADG) in three Egyptian sheep breeds.Materials and Methods:Genomic DNA was extracted from the blood samples of 50 male and female individuals representing Ossimi, Rahmani, and Barki sheep breeds. A 407 bp nucleotide (nt) segment from the first intron of FABP4 was amplified by polymerase chain reaction, sequenced, and analyzed in the different samples.Results:Sequence analysis of the determined segment (407 bp) revealed four SNPs (all transition types) at nt position 372 (CP011894.1:g.57605471) A>G, nt position 211 (CP011894.1:g.57605632) A>G, nt position 143 (CP011894.1:g.57605700) T>C, and nt position 111 (CP011894.1:g.57605732) T>C. The allelic and genotypic frequencies for the identified SNPs in the sheep breeds were calculated. At nt positions 372 and 211, two alleles were identified (A and G). Only two genotypes were present at nt position 372 (AA and AG), while three genotypes were present at nt position 211 (AA, AG, and GG). Two alleles (T and C) and three identified genotypes (TT, TC, and CC) were detected at nt positions 143 and 111. Analysis of the results revealed that AA genotype at nt position 372 is associated with higher estimates for BW, FW, and ADG when compared to all the other genotypes. Very high correlation coefficients were found between the genotypes 143-TT and 111-TT and also between 143-TC and 111-TC. The genotypes 372-AG, 211-GG, 211-AA, 143-TT, 143-CC, 111-TT, 111-TC, and 111-CC were associated with negative effects on BW, FW, and ADG.Conclusion:The detection of four SNPs in a partial sequence of the Egyptian ovine FABP4 gene intron 1 reflected that this gene harbors substantial diversity. In addition, a novel SNP at nt position 372 (CP011894.1:g.57605471) A>G was associated with higher estimates for BW, FW, and ADG.

Effects of polymorphism of myostatin and fatty acid-binding protein 4 genes on the chemical composition of meat in cull female Aceh cattle.

Aim:This study aimed to investigate the association of single nucleotide polymorphism of the myostatin (MSTN) and fatty acid-binding protein 4 (FABP4) genes on the total water, ash, fat, protein, and cholesterol contents of sirloin (gluteus medius muscle) and silverside (biceps femoris muscle) meats of cull female Aceh cattle.Materials and Methods:This analysis covered a total of 27 cull female Aceh cattle slaughtered at the Animal Slaughterhouse of Banda Aceh that was purposively selected based on hair color referred to the criteria described in the Decree of Ministry of Agriculture of the Republic of Indonesia. Genomic DNA was extracted from 25 mg of fresh meat using the spin column method before subjected to a polymerase chain reaction amplification using primer sets specific for 1346-bp and 275-bp fragments of MSTN and FABP4, respectively. A 4-h digestion reaction was done separately for the MSTN/HaeIII and FABP4/NlaIII loci genotyping. The total protein, ash, and fat of the meat were measured using the Indonesian National Standard (SNI) methods whereas its cholesterol content was determined using the AOAC method. The association between each polymorphism and the variation in meat chemical parameters was analyzed using the Pearson correlation test.Results:The results showed that the MSTN/HaeIII locus was polymorphic in Aceh cattle, but the FABP4/NlaIII locus was monomorphic. Meat chemical parameters were not influenced by different commercial cuts and MSTN genotypes, showing that there was no association between different commercial cuts, cattle hair colors, and MSTN/HaeIII and FABP4/NlaIII markers with the meat chemical parameters in Aceh cattle.Conclusion:These results suggest that focusing on the novel effects of MSTN and FABP4 gene polymorphisms on meat production traits might not be useful for marker-assisted selection in Aceh cattle.