One-carbon metabolism and nonalcoholic fatty liver disease: The crosstalk between nutrients, microbiota, and genetics

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Its etiology includes nutritional, genetic, and lifestyle factors. Several mechanisms may link onecarbon metabolism – the associated metabolic pathways of folate, methionine, and choline – to the onset of NAFLD. In this review, we attempted to assess how choline, folate, methionine, and betaine affect NAFLD development, mainly through their role in the secretion of very low-density lipoproteins (VLDL) from the liver. We also reviewed recent articles that have described the relation between microbiota metabolism and NAFLD progression. Moreover, we describe the effect of single-nucleotide polymorphisms (SNP) in genes related to one-carbon metabolism and disease prevalence. We additionally seek SNP identified by genome-wide associations that may increase the risk of this disease. Even though the evidence available is not entirely consistent, it seems that the concentrations of choline, methionine, folate, and betaine may affect the progression of NAFLD. Since there is no effective therapy for NAFLD, further investigations into the link between nutrition, gut microbiota, genetic factors, and NAFLD are still necessary, with a particular emphasis on methyl donors

Maternal protein and folic acid intake during gestation does not program leptin transcription or serum concentration in rat progeny

Maternal nutrition during gestation influences the development of the fetus, thereby determining its phenotype, including nutrient metabolism, appetite, and feeding behavior. The control of appetite is a very complex process and can be modulated by orexigenic and anorexigenic mediators such as leptin, which is involved in the regulation of energy homeostasis by controlling food intake and energy expenditure. Leptin transcription and secretion are regulated by numerous factors, nutrition being one of them. The present study was designed to test whether maternal nutrition can permanently affect leptin gene transcription and leptin serum concentration in rat progeny. Moreover, we analyzed whether leptin expression and secretion in response to high-fat postweaning feeding depends on the maternal diet during gestation. Pregnant rats were fed either a normal protein, normal folic acid diet (the AIN-93 diet); a protein-restricted, normal folic acid diet; a protein-restricted, folic acid-supplemented diet; or a normal protein, folic acid-supplemented diet. After weaning, the progeny was fed either the AIN-93 diet or a high-fat diet. Neither maternal nutrition nor the postweaning diet significantly affected Lep transcription. High-fat feeding after weaning was associated with higher serum leptin concentration, but the reaction of an organism to the fat content of the diet was not determined by maternal nutrition during gestation. There was no correlation between Lep mRNA level and serum leptin concentration. Global DNA methylation in adipose tissue was about 30% higher in rats fed postnatally the high-fat diet (P < 0.01). Our study showed that the protein and folic acid content in the maternal diet had no significant programming effect on Lep transcription and serum leptin concentration in the rats

Folic Acid and Protein Content in Maternal Diet and Postnatal High-Fat Feeding Affect the Tissue Levels of Iron, Zinc, and Copper in the Rat

Although maternal, fetal, and placental mechanisms compensate for disturbances in the fetal environment, any nutritional inadequacies present during pregnancy may affect fetal metabolism, and their consequences may appear in later life. The aim of the present study is to investigate the influence of maternal diet during gestation on Fe, Zn, and Cu levels in the livers and kidneys of adult rats. The study was carried out on the offspring (n = 48) of mothers fed either a protein-balanced or a protein-restricted diet (18% vs. 9% casein) during pregnancy, with or without folic acid supplementation (0.005- vs. 0.002-g folic acid/kg diet). At 10 weeks of age, the offspring of each maternal group were randomly assigned to groups fed either the AIN-93G diet or a high-fat diet for 6 weeks, until the end of the experiment. The levels of Fe, Zn, and Cu in the livers and kidneys were determined by the F-AAS method. It was found that postnatal exposure to the high-fat diet was associated with increased hepatic Fe levels (p < 0.001), and with decreased liver Zn and Cu contents (p < 0.01 and p < 0.05, respectively), as well as with decreased renal Cu contents (p < 0.001). Moreover, the offspring’s tissue mineral levels were also affected by protein and folic acid content in the maternal diet. Both prenatal protein restriction and folic acid supplementation increased the liver Zn content (p < 0.05) and the kidney Zn content (p < 0.001; p < 0.05, respectively), while folic acid supplementation resulted in a reduction in renal Cu level (p < 0.05). Summarizing, the results of this study show that maternal dietary folic acid and protein intake during pregnancy, as well as the type of postweaning diet, affect Fe, Zn, and Cu levels in the offspring of the rat. However, the mechanisms responsible for this phenomenon are unclear, and warrant further investigation

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 individual's 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

Protein and folic acid content in the maternal diet determine lipid metabolism and response to high-fat feeding in rat progeny in an age-dependent manner

Maternal diet during gestation can exert a long-term effect on the progeny’s health by programming their developmental scheme and metabolism. The aim of this study is to analyze the influence of maternal diet on lipid metabolism in 10- and 16-week-old rats. Pregnant dams were fed one of four diets: a normal protein and normal folic acid diet (NP-NF), a protein-restricted and normal folic acid diet (PR-NF), a protein-restricted and folic-acid-supplemented diet (PR-FS), or a normal protein and folic-acid-supplemented diet (NP-FS). We also tested whether prenatal nutrition determines the reaction of an organism to a postweaning high-fat diet. Blood biochemistry and biometrical parameters were evaluated. The expression patterns of PPARα, PPARγ, and LXRα in the liver and adipose tissue were examined by real-time PCR. In the 10-week-old, rats folic acid supplementation of the maternal diet was associated with reduced circulating glucose and total cholesterol concentrations (P < 0.01 and P < 0.001, respectively). Neither prenatal diets nor postnatal feeding affected blood insulin concentrations. In the 16-week-old rats, body weight, abdominal fat mass and central adiposity were reduced in the progeny of the folic acid–supplemented dams (P < 0.01, P < 0.001 and P < 0.01, respectively). Maternal protein restriction had no effect on biometry or blood biochemical parameters. Folic acid supplementation of the maternal diet was associated with reduced expression of PPARα, PPARγ, and LXRα in the liver (P < 0.001). Reduced protein content in the maternal diet was associated with increased PPARα mRNA level in the liver (P < 0.001) and reduced LXRα in adipose tissue (P < 0.01). PPARα and PPARγ transcription in the liver, as well as LXRα transcription in adipose tissue, was also dependent on interaction effects between prenatal and postnatal diet compositions. PPARγ transcription in the liver was correlated with the abdominal fat mass, body weight, and calorie intake, while PPARγ transcription in adipose tissue was correlated with reduced body weight and calorie intake. Total serum cholesterol concentration was correlated with LXRα transcription in the liver. Folic acid supplementation of the maternal diet may have favorable effects for lipid metabolism in the progeny, but these effects are modified by the postnatal diet and age. Furthermore, the expression of LXRα, PPARα, and PPARγ in the liver and adipose tissue largely depends on the protein and folic acid content in the maternal diet during gestation. However, the altered transcription profile of these key regulators of lipid metabolism does not straightforwardly explain the observed phenotype

One-carbon metabolism and nonalcoholic fatty liver disease: The crosstalk between nutrients, microbiota, and genetics

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Its etiology includes nutritional, genetic, and lifestyle factors. Several mechanisms may link onecarbon metabolism – the associated metabolic pathways of folate, methionine, and choline – to the onset of NAFLD. In this review, we attempted to assess how choline, folate, methionine, and betaine affect NAFLD development, mainly through their role in the secretion of very low-density lipoproteins (VLDL) from the liver. We also reviewed recent articles that have described the relation between microbiota metabolism and NAFLD progression. Moreover, we describe the effect of single-nucleotide polymorphisms (SNP) in genes related to one-carbon metabolism and disease prevalence. We additionally seek SNP identified by genome-wide associations that may increase the risk of this disease. Even though the evidence available is not entirely consistent, it seems that the concentrations of choline, methionine, folate, and betaine may affect the progression of NAFLD. Since there is no effective therapy for NAFLD, further investigations into the link between nutrition, gut microbiota, genetic factors, and NAFLD are still necessary, with a particular emphasis on methyl donors

Use of a Smartphone Application Can Improve Assessment of High-Fat Food Consumption in Overweight Individuals

Background: We evaluated the feasibility of an application for measuring the frequency of consumption of high-fat foods and compared this application with standard methods. Methods: Twenty-six females and thirty six males aged 20&#8315;40 were enrolled in Poland. Participants completed the Block Screening Questionnaire for Fat Intake (BSQF; Q1) and a second questionnaire (Q2) with additional high-fat foods. The participants were then monitored for ten days in a real-time manner using a smartphone application that employed the same lists of food as Q2. Results: Most subjects (84%) gave replies to at least three prompts on at least 5 days. The results from Q1 and the application were correlated (r = 0.42, p &lt; 0.001). Energy intake and the frequency of consumption of high-fat foods were correlated in the overweight/obese group (r = 0.83, p &lt; 0.001). The mean differences between Q2 and the app were similar in both groups but the agreement limits were wider in the overweight/obese group than in the normal weight group. Conclusions: An application for mobile devices is a feasible tool for capturing the frequency of high-fat food consumption and it seems to improve the measured variable, especially in overweight or obese people