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

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

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

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

Smoking and dietary inadequacy among Inuvialuit women of child bearing age in the Northwest Territories, Canada

Objective The prevalence of smoking in Aboriginal Canadians is higher than non-Aboriginal Canadians, a behavior that also tends to alter dietary patterns. Compared with the general Canadian population, maternal smoking rates are almost twice as high. The aim of this study was to compare dietary adequacy of Inuvialuit women of childbearing age comparing smokers versus non-smokers. Research methods & procedures A cross-sectional study, where participants completed a culturally specific quantitative food frequency questionnaire. Non-parametric analysis was used to compare mean nutrient intake, dietary inadequacy and differences in nutrient density among smokers and non-smokers. Multiple logistic regression analyses were performed for key nutrients inadequacy and smoking status. Data was collected from three communities in the Beaufort Delta region of the Northwest Territories, Canada from randomly selected Inuvialuit women of childbearing age (19-44 years). Results Of 92 participants, 75% reported being smokers. There were no significant differences in age, BMI, marital status, education, number of people in household working and/or number of self employed, and physical activity between smokers and non-smokers. Non-parametric analysis showed no differences in nutrient intake between smokers and non-smokers. Logistic regression however revealed there was a positive association between smoking and inadequacies of vitamin C (OR = 2.91, 95% CI, 1.17-5.25), iron (OR = 3.16, 95% CI, 1.27-5.90), and zinc (OR = 2.78, 95% CI, 1.12-4.94). A high percentage of women (>60%), regardless of smoking status, did not meet the dietary recommendations for fiber, vitamin D, E and potassium. Conclusions This study provides evidence of inadequate dietary intake among Inuvialuit of childbearing age regardless of smoking behavior

Association of adipocyte genes with ASP expression: a microarray analysis of subcutaneous and omental adipose tissue in morbidly obese subjects

<p>Abstract</p> <p>Background</p> <p>Prevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP) and Triglyceride (TG) (LAT) vs High ASP and TG (HAT). Subcutaneous (SC) and omental (OM) adipose tissues (n = 21) were analysed by microarray, and biologic pathways in lipid metabolism and inflammation were specifically examined.</p> <p>Methods</p> <p>LAT and HAT groups were matched in age, obesity, insulin, and glucose, and had similar expression of insulin-related genes (InsR, IRS-1). ASP related genes tended to be increased in the HAT group and were correlated (factor B, adipsin, complement C3, p < 0.01 each). Differences between LAT and HAT group were almost exclusively in SC tissue, with little difference in OM tissue. Increased C5L2 (p < 0.01), an ASP receptor, in HAT suggests a compensatory ASP pathway, associated with increased TG storage.</p> <p>Results</p> <p>HAT adipose tissue demonstrated increased lipid related genes for storage (CD36, DGAT1, DGAT2, SCD1, FASN, and LPL), lipolysis (HSL, CES1, perilipin), fatty acid binding proteins (FABP1, FABP3) and adipocyte differentiation markers (CEBPα, CEBPβ, PPARγ). By contrast, oxidation related genes were decreased (AMPK, UCP1, CPT1, FABP7). HAT subjects had increased anti-inflammatory genes TGFB1, TIMP1, TIMP3, and TIMP4 while proinflammatory PIG7 and MMP2 were also significantly increased; all genes, p < 0.025.</p> <p>Conclusion</p> <p>Taken together, the profile of C5L2 receptor, ASP gene expression and metabolic factors in adipose tissue from morbidly obese HAT subjects suggests a compensatory response associated with the increased plasma ASP and TG.</p

Like mother, like child : investigating perinatal and maternal health stress in post-medieval London.

Post-Medieval London (sixteenth-nineteenth centuries) was a stressful environment for the poor. Overcrowded and squalid housing, physically demanding and risky working conditions, air and water pollution, inadequate diet and exposure to infectious diseases created high levels of morbidity and low life expectancy. All of these factors pressed with particular severity on the lowest members of the social strata, with burgeoning disparities in health between the richest and poorest. Foetal, perinatal and infant skeletal remains provide the most sensitive source of bioarchaeological information regarding past population health and in particular maternal well-being. This chapter examined the evidence for chronic growth and health disruption in 136 foetal, perinatal and infant skeletons from four low-status cemetery samples in post-medieval London. The aim of this study was to consider the impact of poverty on the maternal-infant nexus, through an analysis of evidence of growth disruption and pathological lesions. The results highlight the dire consequences of poverty in London during this period from the very earliest moments of life