DNA Methylation Changes in Whole Blood and CD16+ Neutrophils in Response to Chronic Folic Acid Supplementation in Women of Childbearing Age.

Folate, a water-soluble vitamin, is a key source of one-carbon groups for DNA methylation, but studies of the DNA methylation response to supplemental folic acid yield inconsistent results. These studies are commonly conducted using whole blood, which contains a mixed population of white blood cells that have been shown to confound results. The objective of this study was to determine if CD16+ neutrophils may provide more specific data than whole blood for identifying DNA methylation response to chronic folic acid supplementation. The study was performed in normal weight (BMI 18.5 - 24.9 kg/m2) women (18 - 35 y; n = 12), with blood samples taken before and after 8 weeks of folic acid supplementation at 800 µg/day. DNA methylation patterns from whole blood and isolated CD16+ neutrophils were measured across >485,000 CpG sites throughout the genome using the Infinium HumanMethylation450 BeadChip. Over the course of the 8-week supplementation, 6746 and 7513 CpG sites changed (p < 0.05) in whole blood and CD16+ neutrophils, respectively. DNA methylation decreased in 68.4% (whole blood) and 71.8% (CD16+ neutrophils) of these sites. There were only 182 CpG sites that changed in both the whole blood and CD16+ neutrophils, 139 of which changed in the same direction. These results suggest that the genome-wide DNA methylation response to chronic folic acid supplementation is different between whole blood and CD16+ neutrophils and that a single white blood cell type may function as a more specific epigenetic reporter of folate status than whole blood.

Biomarkers of Nutrition for Development-Folate Review.

The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development.

Profiles of cognitive functioning in a population-based sample of centenarians using factor mixture analysis.

UNLABELLED: BACKGROUND/STUDY CONTEXT: The goal of the study was to identify and characterize latent profiles (clusters) of cognitive functioning in centenarians and the psychometric properties of cognitive measures within them. METHODS: Data were collected from cross-sectional, population-based sample of 244 centenarians (aged 98 to 108, 15.8% men, 20.5% African American, 38.0% community-dwelling) from 44 counties in northern Georgia participating in the Georgia Centenarian Study (2001-2008). Measures included the Mini-Mental State Examination (MMSE), Severe Impairment Battery (SIB), Wechsler Adult Intelligence Scale-III Similarities subtest (WAIS), Hand Tapping, Behavioral Dyscontrol Scale (BDS), Controlled Oral Word Association Test (COWAT), and Fuld Object Memory Evaluation (FOME). The Global Deterioration Rating Scale (GDRS) was used to independently evaluate criterion-related validity for distinguishing cognitively normal and impaired groups. Relevant covariates included directly assessed functional status for basic and instrumental activities of daily living (DAFS), race, gender, educational attainment, Geriatric Depression Scale Short Form (GDS), and vision and hearing problems. RESULTS: Results suggest two distinct classes of cognitive performance in this centenarian sample. Approximately one third of the centenarians show a pattern of markedly lower cognitive performance on most measures. Group membership is independently well predicted (area under the curve [AUC] = .83) by GDRS scores (sensitivity 67.7%, specificity 82.4%). Membership in the lower cognitive performance group was more likely for individuals who were older, African Americans, had more depressive symptoms, lower plasma folate, carriers of the apolipoprotein E (APOE) ε4 allele, facility residents, and individuals who died in the 2 years following interview. CONCLUSIONS: In a population expected to have high prevalence of dementia, latent subtypes can be distinguished via factor mixture analysis that provide normative values for cognitive functioning. The present study allows estimates for normative cognitive performance in this age group.

25-hydroxyvitamin D status and change in physical performance and strength in older adults: the Health, Aging, and Body Composition Study.

Low 25-hydroxyvitamin D (25(OH)D) concentrations are common among older adults and are associated with poorer physical performance and strength, but results from longitudinal studies have been inconsistent. The 25(OH)D threshold for physical performance and strength was determined, and both cross-sectional and longitudinal associations between 25(OH)D and physical performance and strength were examined, in men and women aged 71-80 years from the Health, Aging, and Body Composition Study (n = 2,641). Baseline serum 25(OH)D was measured in 1998-1999, and physical performance and strength were measured at baseline and at 2- and 4-year follow-up. Piecewise regression models were used to determine 25(OH)D thresholds. Linear regression and mixed models were used to examine cross-sectional and longitudinal associations. The 25(OH)D thresholds were 70-80 nmol/L for physical performance and 55-70 nmol/L for strength. Participants with 25(OH)D <50 nmol/L had poorer physical performance at baseline and at 2- and 4-year follow-up than participants with 25(OH)D ≥75 nmol/L (P < 0.01). Although physical performance and strength declined over 4 years of follow-up (P < 0.0001), in general, the rate of decline was not associated with baseline 25(OH)D. Older adults with low 25(OH)D concentrations had poorer physical performance over 4 years of follow-up, but low 25(OH)D concentrations were not associated with a faster rate of decline in physical performance or strength.

Common genetic variants associate with serum phosphorus concentration.

Phosphorus is an essential mineral that maintains cellular energy and mineralizes the skeleton. Because complex actions of ion transporters and regulatory hormones regulate serum phosphorus concentrations, genetic variation may determine interindividual variation in phosphorus metabolism. Here, we report a comprehensive genome-wide association study of serum phosphorus concentration. We evaluated 16,264 participants of European ancestry from the Cardiovascular Heath Study, Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and the Rotterdam Study. We excluded participants with an estimated GFR <45 ml/min per 1.73 m(2) to focus on phosphorus metabolism under normal conditions. We imputed genotypes to approximately 2.5 million single-nucleotide polymorphisms in the HapMap and combined study-specific findings using meta-analysis. We tested top polymorphisms from discovery cohorts in a 5444-person replication sample. Polymorphisms in seven loci with minor allele frequencies 0.08 to 0.49 associate with serum phosphorus concentration (P = 3.5 x 10(-16) to 3.6 x 10(-7)). Three loci were near genes encoding the kidney-specific type IIa sodium phosphate co-transporter (SLC34A1), the calcium-sensing receptor (CASR), and fibroblast growth factor 23 (FGF23), proteins that contribute to phosphorus metabolism. We also identified genes encoding phosphatases, kinases, and phosphodiesterases that have yet-undetermined roles in phosphorus homeostasis. In the replication sample, five of seven top polymorphisms associate with serum phosphorous concentrations (P < 0.05 for each). In conclusion, common genetic variants associate with serum phosphorus in the general population. Further study of the loci identified in this study may help elucidate mechanisms of phosphorus regulation.

Prevalence and predictors of recommendations to lose weight in overweight and obese older adults in Georgia senior centers.

OBJECTIVE: To examine the prevalence and predictors of health care professional recommendations to lose weight in Older Americans Act Nutrition Program participants in Georgia senior centers who met professional and/or governmental organization criteria for weight loss recommendation. METHODS: Demographic, health, and weight loss recommendation information obtained from community-dwelling convenience sample (n=793; 2007-2008) of older adults via interviewer administered questionnaires. RESULTS: Approximately 70% of participants met weight loss criteria, but only 36% of them received advice to lose weight in the past year. Report of weight loss recommendation was 52.0% for those 'obese with risks' and 19.8% for those 'overweight with risks'. Recommendation to lose weight was significantly (p<0.05) associated with body mass index, waist circumference risk, younger age, self-reported disability, and urban residence. When controlled for other health and demographic factors, recommendation to lose weight was significantly associated with heart disease, but not other chronic conditions including diabetes, hypertension, or joint pain. CONCLUSION: Many older adults who may benefit from weight loss are not receiving advice to do so. Health care professionals need to be aware of this problem to assist community-dwelling older adults in better managing their health to help maintain independence and improve their quality of life.

Effect of clenbuterol on apoptosis, adipogenesis, and lipolysis in adipocytes.

Clenbuterol, a beta(2)-adrenergic receptor (beta(2)-AR) selective agonist, has been shown to decrease body fat in animals and can induce apoptosis in adipose tissue in mice. We hypothesized that direct actions of a beta-adrenergic receptor agonist on adipocytes could trigger the observed apoptotic effect. The hypothesis was inspected by investigating the direct effect of clenbuterol on apoptosis, adipogenesis, and lipolysis in vitro using the 3T3-L1 cell line and rat primary adipocytes. Cells were treated with 10(-9) to 10(-5) M clenbuterol depending on the experiments. There was no apoptotic effect of clenbuterol both in 3T3-L1 cells and rat primary adipocytes. Adipogenesis monitored by Oil Red O staining and AdipoRed assay was modestly decreased by clenbuterol treatment (p < 0.05). In fully differentiated primary adipocytes, clenbuterol increased basal lipolysis compared with the control (p < 0.01). In summary, direct stimulation of beta(2)-AR by clenbuterol does not cause apoptosis in adipocytes, despite a direct lipolytic stimulation and attenuation of adipogenesis.

Cognitive function, physical performance, health, and disease: norms from the georgia centenarian study.

This study provides, for the first time, normative data on cognitive functioning and physical performance, health and health behaviors, and diseases from a population-based sample of 244 centenarians and near-centenarians (M age = 100.5 years, range 98-108, 84.8% women, 21.3% African American) from the Georgia Centenarian Study. Data are presented by the four key dimensions of gender, race, residence, and educational attainment. Results illustrate the profound range of functioning in this age group and indicate considerable differences as a function of each dimension. Bivariate models generally suggest that cognitive functioning and physical performance is higher for men than women; whites than African Americans; community than facility residents; and those with more than high school education than those with less than high school education. Multivariate models elaborate that differences in educational attainment generally account for the largest proportion of variance in cognitive functioning and residential status generally accounts for the largest proportion of variance in physical performance measures. Addition of health variables seldom increases variance accounted for in each domain beyond these four dimensions.

Physical limitations contribute to food insecurity and the food insecurity-obesity paradox in older adults at senior centers in Georgia.

The purpose of this study was to explore the relationship of obesity and physical limitations with food insecurity among Georgians participating in the Older Americans Act (OAA) congregate meal-site program (N = 621, median age = 76 years, 83% female, 36% Black, and 64% White, convenience sample). Food insecurity was assessed using the modified 6-item US Household Food Security Survey Module; obesity was defined as Body Mass Index (BMI) or waist circumference (WC) class I or II obesity; and physical limitations (arthritis, joint pain, poor physical function, weight-related disability) were based on the Disablement Process. A series of multivariate logistic regression models found weight-related disability and obesity (WC class II) may be potential risk factors for food insecurity. Thus, obesity and weight-related disability may be risk factors to consider when assessing the risk of food insecurity and the need for food assistance in this vulnerable subgroup of older adults.

Search for the preadipocyte progenitor cell.

An increase in adipocyte number is a major contributor to the increase in adipose tissue mass that is characteristic of obesity. The identity and regulation of the adipocyte precursor cell (or preadipocyte) and the preadipocyte precursor cell (or progenitor cell) have been intensely studied for many years. In this issue of the JCI, Crossno et al. report that progenitor cells originating from outside the adipose tissue, in particular the bone marrow, can contribute to an increase in adipocyte number (see the related article beginning on page 3220). Their study in mice reveals that treatment with the thiazolidinedione rosiglitazone or exposure to a high-fat diet promotes the trafficking of circulating bone marrow-derived progenitor cells into adipose tissue, where they become multilocular adipocytes. This adds a new and unexpected dimension to this research arena.

Genistein inhibits differentiation of primary human adipocytes.

Genistein, a major soy isoflavone, has been reported to exhibit antiadipogenic and proapoptotic potential in vivo and in vitro. It is also a phytoestrogen which has high affinity to estrogen receptor beta. In this study, we determined the effect of genistein on adipogenesis and estrogen receptor (ER) alpha and beta expression during differentiation in primary human preadipocytes. Genistein inhibited lipid accumulation in a dose-dependent manner at concentrations of 6.25 microM and higher, with 50 microM genistein inhibiting lipid accumulation almost completely. Low concentrations of genistein (3.25 microM) increased cell viability and higher concentrations (25 and 50 microM) decreased it by 16.48+/-1.35% (P<.0001) and 50.68+/-1.34% (P<.0001). Oil Red O staining was used to confirm the effects on lipid accumulation. The inhibition of lipid accumulation was associated with inhibition of glycerol-3-phosphate dehydrogenase activity and down-regulation of expression of adipocyte-specific genes, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, glycerol-3-phosphate dehydrogenase, adipocyte fatty acid binding protein, fatty acid synthase, sterol regulatory element-binding protein 1, perilipin, leptin, lipoprotein lipase and hormone-sensitive lipase. These effects of genistein during the differentiation period were associated with down-regulation of ERalpha and ERbeta expression. This study adds to the elucidation of the molecular pathways involved in the inhibition of adipogenesis by phytoestrogens.

Isolation and culture of preadipocytes from rodent white adipose tissue.

Much of the research devoted to understanding adipose tissue development is currently performed in vitro. Several cell culture models, including preadipocyte cell lines and primary culture of adipose-derived stromal vascular precursor cells, are commonly used to study molecular and cellular events and regulatory influences on preadipocyte proliferation and differentiation. Primary preadipocyte culture systems have several distinct advantages over preadipose cell lines. Because they have not been passaged continuously in culture, primary cultures of adipose derived stromal-vascular (SV) cells more closely reflect the in vivo characteristics of the tissue from which they are derived. In addition, primary cells can be obtained from various adipose tissue depots and from animals at different stages of development, from early postnatal life through advanced age. Cells can also be obtained from genetic rodent models of obesity or from rats and/or mice subjected to nutritional or hormonal manipulation. In each case, specific adipose tissue depots are dissected and the SV cells obtained after collagenase digestion. To examine the effect of tissue source or in vivo or in vitro treatment on preadipocyte proliferation, SV cells are labeled by thymidine incorporation during the exponential growth phase and maintained in culture until sufficiently lipid-filled to allow separation by density. Regulatory influences on various stages of preadipocyte differentiation can be examined in rat SV cultures in a controlled environment featuring chemically defined serum-free medium; whereas, more temperamental mouse SV cultures require the presence of serum for optimal differentiation. Alternatively, preadipocytes differentiated in vitro may be used for examining adipocyte metabolic or secretory responses.

Folate status in women of reproductive age as basis of neural tube defect risk assessment.

Reliable folate status data for women of reproductive age (WRA) to assess global risk for neural tube defects (NTDs) are needed. We focus on a recent recommendation by the World Health Organization that a specific "optimal" red blood cell (RBC) folate concentration be used as the sole indicator of NTD risk within a population and discuss how to best apply this guidance to reach the goal of assessing NTD risk globally. We also emphasize the importance of using the microbiologic assay (MBA) as the most reliable assay for obtaining comparable results for RBC folate concentration across time and countries, the need for harmonization of the MBA through use of consistent key reagents and procedures within laboratories, and the requirement to apply assay-matched cutoffs for folate deficiency and insufficiency. To estimate NTD risk globally, the ideal scenario would be to have country-specific population-based surveys of RBC folate in WRA determined utilizing a harmonized MBA, as was done in recent studies in Guatemala and Belize. We conclude with guidance on next steps to best navigate the road map toward the goal of generating reliable folate status data on which to assess NTD risk in WRA in low- and middle-income countries.

CD4+ and CD8+ T-Cell-Specific DNA Cytosine Methylation Differences Associated With Obesity.

OBJECTIVE: Lifestyle factors associated with obesity may alter epigenome-regulated gene expression. Most studies examining epigenetic changes in obesity have analyzed DNA 5´-methylcytosine (5mC) in whole blood, representing a weighted average of several distantly related and regulated leukocyte classes. To examine leukocyte-specific differences associated with obesity, a pilot study examining 5mC in three distinct leukocyte types isolated from peripheral blood of women with normal weight and obesity was conducted. METHODS: CD4+ T cells, CD8+ T cells, and CD16+ neutrophils were reiteratively isolated from blood, and 5mC levels were measured across >450,000 CG sites. RESULTS: Nineteen CG sites were differentially methylated between women with obesity and with normal weight in CD4+ cells, 16 CG sites in CD8+ cells, and 0 CG sites in CD16+ neutrophils (q < 0.05). There were no common differentially methylated sites between the T-cell types. The amount of visceral adipose tissue was strongly associated with the methylation level of 79 CG sites in CD4+ cells, including 4 CG sites in CLSTN1's promoter, which, this study shows, may regulate its expression. CONCLUSIONS: The methylomes of various leukocytes respond differently to obesity and levels of visceral adipose tissue. Highly significant differentially methylated sites in CD4+ and CD8+ cells in women with obesity that have apparent biological relevance to obesity were identified.

Global folate status in women of reproductive age: a systematic review with emphasis on methodological issues.

Inadequate folate status in women of reproductive age (WRA) can lead to adverse health consequences of public health significance, such as megaloblastic anemia (folate deficiency) and an increased risk of neural tube defect (NTD)-affected pregnancies (folate insufficiency). Our review aims to evaluate current data on folate status of WRA. We queried eight databases and the World Health Organization Micronutrients Database, identifying 45 relevant surveys conducted between 2000 and 2014 in 39 countries. Several types of folate assays were used in the analysis of blood folate, and many surveys used folate cutoffs not matched to the assay. To allow better comparisons across surveys, we attempted to account for these differences. The prevalence of folate deficiency was >20% in many countries with lower income economies but was typically <5% in countries with higher income economies. Only 11 surveys reported the prevalence of folate insufficiency, which was >40% in most countries. Overall, folate status data for WRA globally are limited and must be carefully interpreted due to methodological issues. Future surveys would benefit from using the microbiologic assay to assess folate status, along with assay-matched cutoffs to improve monitoring and evaluation of folic acid interventions, thus informing global efforts to prevent NTDs.

Association between one-carbon metabolism indices and DNA methylation status in maternal and cord blood.

One-carbon metabolism is essential for multiple cellular processes and can be assessed by the concentration of folate metabolites in the blood. One-carbon metabolites serve as methyl donors that are required for epigenetic regulation. Deficiencies in these metabolites are associated with a variety of poor health outcomes, including adverse pregnancy complications. DNA methylation is known to vary with one-carbon metabolite concentration, and therefore may modulate the risk of adverse pregnancy outcomes. This study addresses changes in one-carbon indices over pregnancy and the relationship between maternal and child DNA methylation and metabolite concentrations by leveraging data from 24 mother-infant dyads. Five of the 13 metabolites measured from maternal blood and methylation levels of 993 CpG sites changed over the course of pregnancy. In dyads, maternal and fetal one-carbon concentrations were highly correlated, both early in pregnancy and at delivery. The 993 CpG sites whose methylation levels changed over pregnancy in maternal blood were also investigated for associations with metabolite concentrations in infant blood at delivery, where five CpG sites were associated with the concentration of at least one metabolite. Identification of CpG sites that change over pregnancy may result in better characterization of genes and pathways involved in maintaining a healthy, term pregnancy.

Serum 25-Hydroxyvitamin D and Intact Parathyroid Hormone Influence Muscle Outcomes in Children and Adolescents.

Increases in 25-hydroxyvitamin D concentrations are shown to improve strength in adults; however, data in pediatric populations are scant and equivocal. In this ancillary study of a larger-scale, multi-sited, double-blind, randomized, placebo-controlled vitamin D intervention in US children and adolescents, we examined the associations between changes in vitamin D metabolites and changes in muscle mass, strength, and composition after 12 weeks of vitamin D3 supplementation. Healthy male and female, black and white children and adolescents between the ages of 9 and 13 years from two US states (Georgia 34°N and Indiana 40°N) were enrolled in the study and randomly assigned to receive an oral vitamin D3 dose of 0, 400, 1000, 2000, or 4000 IU/d for 12 weeks between the winter months of 2009 to 2011 (N = 324). Analyses of covariance, partial correlations, and regression analyses of baseline and 12-week changes (post-baseline) in vitamin D metabolites (serum 25(OH)D, 1,25(OH)2 D, intact parathyroid hormone [iPTH]), and outcomes of muscle mass, strength, and composition (total body fat-free soft tissue [FFST], handgrip strength, forearm and calf muscle cross-sectional area [MCSA], muscle density, and intermuscular adipose tissue [IMAT]) were assessed. Serum 25(OH)D and 1,25(OH)2 D, but not iPTH, increased over time, as did fat mass, FFST, forearm and calf MCSA, forearm IMAT, and handgrip strength (p < 0.05). Vitamin D metabolites were not associated with muscle strength at baseline nor after the 12-week intervention. Changes in serum 25(OH)D correlated with decreases in forearm IMAT, whereas changes in serum iPTH predicted increases in forearm and calf MCSA and IMAT (p < 0.05). Overall, increases in 25(OH)D did not influence muscle mass or strength in vitamin D-sufficient children and adolescents; however, the role of iPTH on muscle composition in this population is unknown and warrants further investigation. © 2018 American Society for Bone and Mineral Research.

A prospective analysis of plasma 25-hydroxyvitamin D concentrations in white and black prepubertal females in the southeastern United States.

BACKGROUND: Little is known regarding changes in vitamin D status among children living in the southern United States and whether these changes are race-dependent. OBJECTIVES: The aims were to prospectively assess plasma 25-hydroxyvitamin D [25(OH)D] concentrations in prepubertal black and white girls (n = 83) living in northeast Georgia and to determine whether 25(OH)D concentrations change with increasing age. DESIGN: Plasma samples were obtained annually over a time frame of 1-7 y, and 25(OH)D concentrations were assessed by using radioimmunoassay. Percentage body fat (%BF) and fat-free soft tissue (FFST) mass were measured by using dual-energy X-ray absorptiometry. Linear mixed-effects models were used with height, weight, body mass index percentile, %BF, FFST, pubertal stage, dietary intake, physical activity, and socioeconomic status as covariates. RESULTS: Plasma 25(OH)D values < 80 nmol/L were observed in 75% of the participants. Plasma 25(OH)D values (analyzed on the natural logarithm scale) decreased with increasing age (P = 0.02), independent of race. Plasma 25(OH)D values were higher in whites than in blacks (P < 0.0001), and the amount of this difference depended on season (P < 0.001 for all seasons). A significant negative association between FFST and 25(OH)D, beyond the effects of age, race, and season (P = 0.007), was observed. The effects of age, race, and season on 25(OH)D remained significant when dietary calcium, vitamin D, and physical activity were used as covariates; however, after adjustment for FFST, only the effects of race and season remained. CONCLUSIONS: White girls living in the southeastern United States have higher 25(OH)D concentrations than do black girls, and the magnitude of this difference depends on the season. Decreases in 25(OH)D with age are associated with increases in FFST. Whether FFST requires additional vitamin D during growth remains to be determined.

Distinctions in gene-specific changes in DNA methylation in response to folic acid supplementation between women with normal weight and obesity.

BACKGROUND/OBJECTIVES: Obesity and maternal folate deficiency are associated with increased risk for neural tube defects (NTDs). Limited knowledge exists on the impact of folate status or obesity on DNA methylation of genes related to NTD risk and folate metabolism. SUBJECTS/METHODS: Women (18-35y) with normal weight (NW; BMI 18.5-24.9kg/m2; n=12) and obesity (OB; BMI >30kg/m2; n=6) were provided FA (800µg/d) for 8-weeks. Serum folate concentration and changes in DNA methylation across 2098 CpG sites in 91 genes related to NTD risk and folate metabolism were examined. RESULTS: Serum folate concentration increased in both groups following FA supplementation, but OB maintained a relative lower concentration (NW; 38.36±2.50-71.41±3.02nmol/L and OB; 27.12±3.09-56.85±3.90nmol/L). Methylation of 56 and 99 CpG sites changed in response to supplementation in NW and OB, respectively, and majority of these sites decreased in methylation in both groups. Only 4 CpG sites responded to supplementation in both groups. Gene ontology analysis revealed a response to supplementation in 61 biological processes (BPs) from the selected genes. Five of the 61 BPs were identified only in NW, including neural tube closure, while 13 of the 61 BPs were enriched only in OB, including folate metabolism, vitamin B12 metabolism and methylation related processes. CONCLUSIONS: Changes in DNA methylation in genes related to NTD risk and folate metabolism in response to FA supplementation were different in NW and OB. Increased NTD risk and abnormal folate metabolism in obesity may be due to a distinctive epigenetic response to folate status in these genes.

Associations among osteocalcin, leptin and metabolic health in children ages 9-13 years in the United States.

BACKGROUND: This study aimed to investigate the relationships among osteocalcin, leptin and metabolic health outcomes in children ages 9-13 years. METHODS: This was a cross-sectional analysis of baseline data from 161 boys and 157 girls (ages 9-13 years) who previously participated in a double-blinded randomized placebo controlled trial of vitamin D supplementation. Relationships among fasting serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), leptin, and metabolic health outcomes were analyzed. RESULTS: Approximately 52% of study participants were obese based on percent body fat cutoffs (>25% for boys and >32% for girls) and about 5% had fasting serum glucose within the prediabetic range (i.e. 100 to 125 mg/dL). Serum tOC was not correlated with leptin, glucose, insulin, HOMA-IR, or HOMA-ß after adjusting for percent body fat. However, serum ucOC negatively correlated with leptin (partial r = -0.16; p = 0.04) and glucose (partial r = -0.16; p = 0.04) after adjustment for percent body fat. Leptin was a positive predictor of insulin, glucose, HOMA-IR, and HOMA-ß after adjusting for age, sex and percent body fat (all p < 0.001). CONCLUSIONS: These data depict an inverse relationship between leptin and various metabolic health outcomes in children. However, the notion that tOC or ucOC link fat with energy metabolism in healthy children was not supported. CLINICAL TRIAL REGISTRATION NUMBER: NCT00931580.