Agata Chmurzynska

The multigene family of fatty acid-binding proteins (FABPs): Function, structure and polymorphism

Fatty acid-binding proteins (FABPs) are members of the superfamily of lipid-binding proteins (LBP). So far 9 different FABPs, with tissue-specific distribution, have been identified: L (liver), I (intestinal), H (muscle and heart), A (adipocyte), E (epidermal), Il (ileal), B (brain), M (myelin) and T (testis). The primary role of all the FABP family members is regulation of fatty acid uptake and intracellular transport. The structure of all FABPs is similar — the basic motif characterizing these proteins is β-barrel, and a single ligand (e.g. a fatty acid, cholesterol, or retinoid) is bound in its internal water-filled cavity. Despite the wide variance in the protein sequence, the gene structure is identical. The FABP genes consist of 4 exons and 3 introns and a few of them are located in the same chromosomal region. For example,A-FABP, E-FABP andM-FABP create a gene cluster. Because of their physiological properties some FABP genes were tested in order to identify mutations altering lipid metabolism. Furthermore, the porcineA-FABP andH-FABP were studied as candidate genes with major effect on fatness traits.

Fetal programming: link between early nutrition, Dna methylation, and complex diseases

Complex traits, including those involved in diet-related diseases, are determined by multiple genes and environmental influences. Factors influencing the development of complex traits should be expanded to include epigenetic factors, such as DNA methylation, which occurs in utero. Epigenetic factors regulate gene expression and thereby cell differentiation and organogenesis. The process of epigenotype establishment is sensitive to environmental conditions, with nutrition being one of the most important related factors. For example, DNA methylation depends on the availability of several nutrients including methionine and vitamins B(6), B(12), and folate. Epidemiological studies show that undernutrition during fetal life is associated with increased susceptibility to complex diseases. Numerous studies have been conducted on prenatal caloric and protein undernutrition. A reduction in the number of cells and changes in the structure and functioning of organs, as well as permanent changes in DNA methylation and gene expression, have been considered the molecular mechanisms responsible for metabolism programming.

Polymorphism of genes encoding homocysteine metabolism-related enzymes and risk for cardiovascular disease.

The aim of this review is to present a general overview of the relationships among homocysteine metabolism, polymorphism of the genes encoding homocysteine metabolism-related enzymes, and the nutrients influencing the plasma homocysteine level. Combining these factors creates a profile of an individuals susceptibility to complex diseases associated with hyperhomocysteinemia. Homocysteine is an amino acid derived from the demethylation of methionine. Hyperhomocysteinemia is associated with an increased risk of several complex diseases, including cardiovascular diseases. The level of plasma homocysteine depends on the combined effects of genetic and environmental factors. Polymorphisms of genes encoding homocysteine metabolism-related enzymes, such as methylenetetrahydrofolate reductase, methionine synthase, methionine synthase reductase, and cystathionine beta-synthase, influence plasma homocysteine concentration and thereby cardiovascular health. On the other hand, homocysteine metabolism may be modulated by dietary intake of the nutrients involved in homocysteine metabolism (ie, folates, vitamin B(6), and vitamin B(12)). Thus, the appropriate health-promoting doses of these nutrients may vary among certain groups of individuals, depending on their genotypes and other risk factors for complex diseases. Better understanding of the relationship between genotype and nutrition influencing the plasma total homocysteine level and cardiovascular health may improve the cardiovascular diagnostic tests (ie, measurement of biologic markers). It could be possible to define the level of progression, severity, and susceptibility to disease much earlier than it is done now. In conclusion, the introduction of combined dietary and pharmacologic treatment would be possible at the initial stages of disease.

Cytogenetic mapping of DGAT1, PPARA, ADIPOR1 and CREB genes in the pig.

In the present study we show FISH localization of 4 porcine BAC clones harbouring potential candidate genes for fatness traits:DGAT1 (SSC4p15),PPARA (SSC5p15),ADIPOR1 (SSC10p13) andCREB (SSC15q24). Until now theCREB andADIPOR1 genes are considered to be monomorphic,DGAT1 is highly polymorphic, while for thePPARA gene only 1 SNP was identified. Assignment of the studied genes in relation to QTL chromosome regions for meat quality in pig chromosomes SSC4, SSC5, SSC10 and SSC15 is discussed.

Cytogenetic mapping of eight genes encoding fatty acid binding proteins (FABPs) in the pig genome.

In the present study cytogenetic localization of eight fatty acid binding protein genes in the pig genome was shown. BAC clones, containing sequences of selected genes (FABP1, FABP2, FABP3, FABP4, FABP5, FABP6, FABP7 and FABP8) were derived from porcine BAC libraries and mapped by FISH to porcine chromosomes (SSC) 3q12, 8q25, 6q26, 4q12, 4q12, 16q22, 1p22 and 4q12, respectively. Detailed analyses of regions containing gene clusters (FABP4, FABP5, FABP8) in chromosome 4 were performed and their order was established. It was shown that these three genes are located beyond the FAT1 region. Assignment of the FABP genes to chromosome regions harboring quantitative trait loci (QTL) for fat deposition is discussed.

Guide for Current Nutrigenetic, Nutrigenomic, and Nutriepigenetic Approaches for Precision Nutrition Involving the Prevention and Management of Chronic Diseases Associated with Obesity

Chronic diseases, including obesity, are major causes of morbidity and mortality in most countries. The adverse impacts of obesity and associated comorbidities on health remain a major concern due to the lack of effective interventions for prevention and management. Precision nutrition is an emerging therapeutic approach that takes into account an individuals genetic and epigenetic information, as well as age, gender, or particular physiopathological status. Advances in genomic sciences are contributing to a better understanding of the role of genetic variants and epigenetic signatures as well as gene expression patterns in the development of diverse chronic conditions, and how they may modify therapeutic responses. This knowledge has led to the search for genetic and epigenetic biomarkers to predict the risk of developing chronic diseases and personalizing their prevention and treatment. Additionally, original nutritional interventions based on nutrients and bioactive dietary compounds that can modify epigenetic marks and gene expression have been implemented. Although caution must be exercised, these scientific insights are paving the way for the design of innovative strategies for the control of chronic diseases accompanying obesity. This document provides a number of examples of the huge potential of understanding nutrigenetic, nutrigenomic, and nutriepigenetic roles in precision nutrition.

Association of a New SNP in Promoter Region of the Porcine FABP3 Gene with Fatness Traits in a Polish Synthetic Line

Associations between FABP3 (alternatively named H-FABP) gene polymorphisms and fatness traits were tested in two pig breeds (Polish Large White and Polish Landrace) and one synthetic line—990. Three known single nucleotide polymorphisms, detected by HinfI, MspI and HaeIII restriction enzymes, were analyzed. Moreover, three new polymorphisms in the 5′ regulatory region were identified: C(–221)T, C(–160)G and T(−158)G, but only the third one was widely distributed and correlated with backfat thickness in line 990. The obtained results suggest that the FABP3 gene is linked with an unknown gene directly affecting backfat thickness, but the analyzed polymorphisms do not influence fatness traits.

Chromosomal localization of nine porcine genes encoding transcription factors involved in adipogenesis.

Chromosomal localization of nine porcine genes encoding transcription factors involved in adipogenesis was determined. BAC clones harboring sequences of selected genes CEBPA (SSC6q12), CEBPB (SSC17q23), CEBPD (SSC4q15), CEBPG (SSC6q12), PPARG (SSC13q24), SREBF1 (SSC10q17), DDIT3 (SSC12q15), GATA2 (SSC13q24 →q31) and GATA3 (SSC5p12) were mapped by FISH. The positions of these genes in the human and pig genomes were compared. A potential role of the genes encoding adipogenesis factors as candidate genes for fatness traits as well as obesity-related phenotypes is discussed.

Dietary, anthropometric, and biochemical factors influencing plasma choline, carnitine, trimethylamine, and trimethylamine-N-oxide concentrations.

Abstract The objective of the study was to evaluate the nutritional, anthropometric, and biochemical factors that influence choline, l-carnitine, trimethylamine (TMA), and trimethylamine-N-oxide (TMAO) metabolism in elderly women. The volunteers’ diet was assessed using a food frequency questionnaire. Dietary patterns were estimated using a self-established score method. Body mass index (BMI), serum glucose, total, HDL, LDL cholesterol, triacylglycerol, homocysteine (tHcy), free choline (fchol), L-carnitine, TMA, and TMAO were assessed. Higher concentrations of l-carnitine, fchol, and TMAO were found in those women who had more western-style dietary patterns. Nor choline or betaine intake affected plasma fchol, TMA, or TMAO. BMI was positively correlated with fchol and TMA. tHcy was positively correlated with fchol, TMA, and TMAO, while fchol was also positively correlated with TMA and TMAO. Dietary patterns and plasma tHcy concentration influence fchol, TMA, and TMAO plasma concentration. Plasma TMA and fchol may be associated with BMI.

Homocysteine homeostasis in the rat is maintained by compensatory changes in cystathionine β-synthase, betaine-homocysteine methyltransferase, and phosphatidylethanolamine N-methyltransferase gene transcription occurring in response to maternal protein and folic acid intake during pregnancy and fat intake after weaning

The reactions of the methionine/homocysteine pathway are mediated by several enzymes, including phosphatidylethanolamine N-methyltransferase, cystathionine β-synthase, and betaine-homocysteine methyltransferase. Homocysteine homeostasis is regulated by these enzymes. We hypothesized here that the protein and folic acid content in the maternal diet affects methionine/homocysteine metabolism in the progeny. To test this hypothesis, pregnant rats were fed a diet with normal protein and normal folic acid levels (a modified casein-based AIN-93G diet), a protein-restricted and normal folic acid diet, a protein-restricted and folic acid-supplemented diet, or a normal protein and folic acid-supplemented diet. The progeny were fed either the modified AIN-93G diet or a high-fat lard-based diet. Progeny were analyzed for expression of the phosphatidylethanolamine N-methyltransferase, cystathionine β-synthase, and betaine-homocysteine methyltransferase genes in the liver and for serum homocysteine concentration. Interactions between prenatal and postnatal nutrition were also determined. The progeny of the dams fed the diets supplemented with folic acid showed decreased expression of all 3 genes (P < .001). An interaction effect between the protein and folic acid content in the maternal diet contributed to this down-regulation (P < .001), and the postweaning diet modified these effects. Serum homocysteine concentrations were approximately 15% higher in the male rats (P < .01), but neither prenatal nutrition nor the postweaning diet affected it significantly. We conclude that maternal diet during gestation has an important effect on the transcription level of these 3 genes, but changes in gene expression were not associated with significant changes in progeny homocysteine concentrations.