Analysing food groups and nutrient intake in adults who met and did not meet the daily recommended vegetable intake of 350 g: the 2016 National Health and Nutrition Survey in Japan.

This study aimed to compare the differences in the intake of food groups and nutrients between Japanese adults who consumed the recommended daily vegetable intake (350 g/day) and those who did not. Dietary information was obtained from one-day dietary records collected from the 2016 National Health and Nutrition Survey, which was conducted in 46 prefectures in Japan. The participants aged ≥20 years (n = 21,606; 53.8% women) were classified into the < and ≥350 g/day groups. Inter-group differences for 17 food groups and 27 nutrients were assessed as percentages of consumers (food groups only) and energy-adjusted intake (units/MJ/d or % of total energy intake). Overall, 29% of participants consumed ≥350 g/day of vegetables. The ≥350 g/day group had a higher percentage of consumers and energy-adjusted intakes for all vegetable subgroups than the <350 g/day group. For other food groups, the ≥350 g/day group had higher percentages of consumers for all food groups, except for cereals, eggs, and condiments and seasonings, which showed no significant differences. However, the ≥350 g/day group had a significantly higher energy-adjusted intake for potatoes and other tubers, mushrooms, meats, and condiments and seasonings but a significantly lower value for cereals, eggs, savoury snacks and confectionaries, and beverages. The ≥350 g/day group had a significantly higher intake of almost all (25/27) nutrients, including sodium, than the <350 g/day group. Participants with vegetable intake ≥350 g/day might have a more favourable intake of food groups and nutrients; however, watching for salt intake is necessary when promoting vegetable intake.

[Corrigendum: How accurate are self-reported anthropometrics among the Japanese? A scoping review].

　Nihon Koshu Eisei Zasshi(JAPANESE JOURNAL OF PUBLIC HEALTH), Vol. 70 (2023) No. 12 pp.817-827.

[How accurate are self-reported anthropometrics among the Japanese? A scoping review].

Objectives　Monitoring of obesity and underweight prevalence in general populations is crucial for the implementation of effective public health measures. Self-reported height and weight values are often used to assess the body mass index (BMI) in such epidemiological surveillance. However, it is known that using self-reported height and weight may underestimate the prevalence of obesity (BMI≥25 kg/m2), while its accuracy for underweight (BMI<18.5 kg/m2) prevalence is not well-understood. The aim of this study was to conduct a scoping review on the accuracy of self-reported anthropometrics in the Japanese population, where both obesity and underweight are prevalent.Methods　Using PubMed and CiNii Research, a literature search was conducted for studies published in English or Japanese by 2022 that were conducted in Japan and compared self-reported and measured height, weight, or/and BMI. The study design and mean reported errors (mean of reported values－mean of measured values) were extracted and tabulated, and differences by BMI categories were also considered.Results　A total of 17 studies, with 11 being published in English, were included in this review. These studies were conducted in nationwide cohort studies (n=4), local populations (n=4), workplaces (n=3), and educational institutions (n=6), with diverse age ranges (10-91 years) and sample sizes (<100 to >30,000). Although the degree of mean reporting error varied between studies, most of the studies reported that height was overreported, weight was underreported, and BMI was underestimated. In the three studies that reported mean reporting errors by BMI category, the direction of reporting error for height remained consistent across all body size categories, while weight and BMI were overreported and overestimated only among the underweight. Four studies in adults showed that 14.2-37.6% of actually obese individuals and 11.1-32.3% of underweight individuals were misclassified as 'normal range' (18.5≤BMI<25 kg/m2) based on self-reporting, while 0.8-5.4% and 1.2-4.1% of individuals actually within the normal range were misclassified as 'underweight' and 'obese' based on self-report, respectively.Conclusion　This study suggests that using BMI based on self-reported height and weight can underestimate the prevalence of both obesity and underweight in the Japanese population. These biases should be taken into consideration when using self-reported anthropometrics in epidemiological studies.

Interleukin-19 Gene-Deficient Mice Promote Liver Fibrosis via Enhanced TGF-ß Signaling, and the Interleukin-19-CCL2 Axis Is Important in the Direction of Liver Fibrosis.

IL-19 is a cytokine discovered by homologous searching with IL-10 and is produced by non-immune cells, such as keratinocytes, in addition to immune cells, such as macrophages. Liver fibrosis results from the inflammation and activation of hepatic stellate cells via chronic liver injury. However, the participation of IL-19 in liver fibrosis remains to be sufficiently elucidated. Our group studied the immunological function of IL-19 in a mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis. IL-19 gene-deficient (KO) mice and body weight-matched wild-type (WT) mice were used. A liver fibrosis mouse model was created via CCl4 administration (two times per week) for 8 weeks. In CCl4-induced liver fibrosis, serum analysis revealed that IL-19 KO mice had higher ALT levels compared to WT mice. IL-19 KO mice had worse fibrosis, as assessed by morphological evaluation of total area stained positive with Azan and Masson trichrome. In addition, the expression of α-SMA was increased in liver tissues of IL-19 KO mice compared to WT mice. Furthermore, mRNA expression levels of TGF-ß and α-SMA were enhanced in IL-19 KO mice compared to WT mice. In vitro assays revealed that IL-19-high expressing RAW264.7 cells inhibited the migration of NIH3T3 cells via the inhibited expression of CCL2 in the presence of CCl4 and IL-4. These findings indicate that IL-19 plays a critical role in liver fibrosis by affecting TGF-ß signaling and the migration of hepatic stellate cells during liver injury. Enhancement of the IL-19 signaling pathway is a potential treatment for liver fibrosis.

Trapa bispinosa Roxb. Pericarp Extract Exerts 5α-Reductase Inhibitory Activity in Castrated Benign Prostatic Hyperplasia Model Mice.

Trapa bispinosa Roxb. pericarp extract (TBE) has a polyphenol-rich composition and exhibits potent antioxidant and anti-glycation activities in vitro. In the present study, we investigated the inhibitory effects of TBE on 5α-reductase in vitro using LNCaP cells and in vivo using a mouse model of castrated benign prostatic hyperplasia. TBE showed concentration-dependent inhibitory effects in the 5α-reductase (5αR) activity assay. In a reporter assay using AR-Luc/LNCaP cells, TBE inhibited the activity induced by testosterone, but not that induced by dihydrotestosterone. TBE also suppressed prostate cell proliferation, prostate-specific antigens, and transmembrane protease serine 2 expression in a castrated benign prostatic hyperplasia mouse model. In addition, ellagic acid, but not gallic acid, decreased 5αR and AR-Luc activities. Together, these results suggest a potential role for TBE in benign prostatic hyperplasia through inhibition of 5αR.

Diet Quality and Its Relationship with Weight Characteristics in Pregnant Japanese Women: A Single-Center Birth Cohort Study.

Maternal underweight and inadequate gestational weight gain (GWG) are problems in Japan. However, increases in food intake aimed at weight gain alone are not sufficient for mother-child health. This study assessed diet quality based on the 3-day dietary records of pregnant women in an urban area of Japan in order to show the importance of evaluating diet quality, using the Nutrient-Rich Food Index 9.3 (NRF9.3), which is one metric based on nutrition profiling, and the Japanese Food Guide Spinning Top (JFGST). After excluding misreporters of energy intake, we stratified women (n = 91) by pre-pregnancy body mass index (BMI) and determined energy intake, diet quality status, and their relationship with GWG. Intakes of carbohydrate-containing staple foods, vegetable dishes, and fruit were insufficient regardless of BMI. Most of the underweight women with inadequate GWG had insufficient energy intake but high diet quality, as assessed by NRF9.3. In contrast, most women who consumed energy within the recommended range had low diet quality and gained weight at inappropriate levels. These results highlight the importance for pregnant Japanese women to maintain diet quality through a nutrient-dense diet, while simultaneously increasing energy intake after evaluation of their individual diet quality.

Determinants of handgrip strength at age 2 years in children born moderate and late preterm and associations with neurodevelopmental outcomes.

BACKGROUND: Handgrip strength (HGS) indicates current and future health. Although preterm infants have an increased risk of poor grip strength in later life, its determinants and relationship with neurodevelopment are not well understood. AIMS: To determine HGS in children born preterm and explore the relationship of HGS with demography, anthropometry, nutritional factors, and neurodevelopmental outcomes. STUDY DESIGN: A prospective cohort study of moderate-late preterm babies enrolled in a randomised trial of nutritional support strategies, the DIAMOND trial. SUBJECTS: A total of 116 children born between 32 and 35 weeks' gestation, whose HGS was measured at 2 years' corrected age. OUTCOME MEASURES: HGS was measured using a dynamometer, and neurodevelopment was assessed using the Bayley Scales of Infant Development-III. Anthropometry and body composition were assessed at birth, discharge, and at 4 months' and 2 years' corrected age. Information on demographics and breastfeeding practices, including type of milk at discharge and duration of exclusive breastfeeding, was collected using questionnaires. RESULTS: The mean (standard deviation) HGS was 2.26 (1.07) kg. The Bayley scores were < 85 (-1 standard deviation) in 6 %, 20 %, and 1 % for the cognitive, language, and motor scales, respectively. Multiple regression analysis revealed that HGS was positively associated with language and motor scores (p < .05) after adjusting for confounding factors. HGS was not associated with sex, anthropometry, body composition, or breastfeeding practices. Maternal education was independently associated with HGS (p < .01). CONCLUSIONS: HGS at age 2 years in children born moderate-late preterm is associated with language and motor development and maternal education level.

Monitoring the Consumption of Vegetables among OECD Countries, Including Japan.

Increasing intakes of vegetables are associated with risk reduction in various non-communicable diseases, especially cardiovascular disease. In order to compare the proportion of daily vegetable intake among adults from these 30 Organization for Economic Co-operation and Development (OECD) countries as well as Japan, we applied data from the OECD website and the 2017 National Health and Nutrition Survey, Japan (NHNS-J). The figures for Australia, Israel, Korea, New Zealand, and the United States exceeded 80%, where survey questions in these countries asked the amount of intake, instead of the frequency of intake. In Japan, results from the one-day dietary record showed that 99.2% of adults consumed vegetables on the survey day; however, this decreased to 66.3% when assessed by a qualitative question. Proportion of daily vegetable intake as well as average intake amount was higher among those aged 60 y or older. Health policies to increase vegetable intake should target younger age groups to promote health in future generations, in Japan.

Does earlier acquisition of motor competence promote pubertal physical activity in Japanese elementary school children: A 4-year follow-up study.

This 4-year follow-up study investigated which profile of motor competence (MC) in early childhood more strongly correlated with moderate-to-vigorous physical activity (MVPA) in early pubescence. A total of 247 first-grade children (152 boys) aged 6 to 7 years old participated in the baseline measurement. MVPA was measured using an accelerometer annually until the fifth grade. Body fat percentage was assessed using dual-energy X-ray absorptiometry at baseline. MC included fundamental movement skills (FMS) and motor performance, which were assessed in terms of locomotor and object control. FMS was assessed by the Test of Gross Motor Development-2, while motor performance (locomotor: run, hop, jump, and side-step, object control: throw, kick, and hand dribble) was assessed by Japanese Physical Fitness and Motor Abilities Test at baseline. Multiple regression analysis showed that locomotor and object control performance were significant predictors of MVPA in later grades in boys but not in girls. These associations between locomotor performance and MVPA mainly remained significant after controlling for body fat and MVPA at baseline. FMS in both genders was not a significant predictor of MVPA in early pubescence. This study suggests that appropriate strategies for increasing MVPA from prepubescence to early pubescence may differ between boys and girls.

Weight Gain and Nutrition during Pregnancy: An Analysis of Clinical Practice Guidelines in the Asia-Pacific Region.

Nutrition and weight gain during pregnancy can influence the life-course health of offspring. Clinical practice guidelines play an important role in ensuring appropriate nutrition and weight gain among pregnant women. This study aims to identify clinical practice guidelines on gestational weight gain and/or maternal nutrition across the Asia-Pacific region and to determine the quality of the guidelines and variability in the recommendations. Through a systematic search of grey literature from 38 Asia-Pacific countries, 23 published guidelines were obtained. Of these, 10 eligible clinical practice guidelines reporting nutrition- or/and weight-related recommendations for pregnant women were selected and reviewed. Guideline quality was determined using the Assessment of Guidelines for Research Evaluation II (AGREE II) instrument. Of the 10 guidelines, 90% were classified as low-quality in the AGREE II appraisal. Several variations were found with respect to recommendations on gestational weight gain, including those specific to Asian populations. The recommendations on dietary advice, additional energy intake, and nutritional supplementation during pregnancy were varied. Clinical practice guidelines on weight gain and nutrition in pregnancy across the Asia-Pacific region are generally of poor quality, reflecting significant variation, and need to be improved to ensure pregnant women receive appropriate advice. (PROSPERO registration no. CRD42021291395).

Association Between Age of Achieving Gross Motor Development Milestones During Infancy and Body Fat Percentage at 6 to 7 Years of Age.

OBJECTIVES: The later achievement of gross motor milestones during infancy is associated with adiposity in early childhood. However, the associations between gross motor development and adiposity after entering primary school are unclear. This study examined the associations between the ages at which six gross motor milestones were achieved and adiposity during early school years. METHODS: This retrospective study was conducted in 2012 and 2013. Data were collected from 225 first-grade primary school children (mean age, 6.9 years; 39% girls). Adiposity was assessed using dual-energy X-ray absorptiometry and expressed as body fat percentage. Data describing the ages of achieving six gross motor milestones (holding head up, sitting, crawling, standing supported, walking supported, and independent walking) were obtained from the Maternal and Child Health Handbooks. RESULTS: Mean body fat percentage was 21.7%. Multiple linear regression analyses revealed that later ages of achieving crawling (p < .001 [95% confidence interval: 0.33-1.16]), standing supported (p < .001 [95% confidence interval: 0.64-1.65]), and walking supported [p = .013 (95% confidence interval: 0.13-1.07)] were associated with increased fat. However, the ages of achieving holding head up (p = .053), sitting (p = .175), and independent walking (p = .736) were not statistically significant. CONCLUSIONS: Achieving crawling, standing supported, and walking supported later predict increased body fat when aged 6-7 years. The practice of observing gross motor milestone achievements may allow early targeted interventions to optimize body composition before beginning school and thereby, potentially prevent childhood obesity.

Trimester-specific associations between extracellular vesicle microRNAs and fetal growth.

OBJECTIVE: Placenta-derived extracellular vesicles and their cargoes, especially microRNAs (EV-miRNAs), may contribute to fetal and placental development. During pregnancy, the levels of several maternal blood EV-miRNAs, including miRNAs of placental origin, vary among individuals and change throughout gestation. However, the effects of these miRNAs on fetal growth and trimester-specificity have not been fully elucidated. The purpose of this study is to test the hypothesis that the serum levels of two extracellular vesicles (EV)-miRNAs (miR-127-3p and miR-26b-5p), which may be involved in fetoplacental regulation, would be significantly associated with fetal growth in a trimester-specific manner. MATERIALS AND METHODS: This is a single-center birth cohort of maternal serum samples obtained at both the second and third trimesters. To minimize the influence of confounding factors, the analysis was limited to singleton vaginal deliveries, resulting in 27 participants being included in this study. EV RNAs were isolated using a membrane affinity method, and the relative expression levels of miR-127-3p and miR-26b-5p were measured using the RT-qPCR method with miR-484 as control. The associations between the two EV-miRNAs and fetal and placental growth were evaluated using a linear regression model and compared between the two trimesters. RESULTS: EV-miR-127-3p levels tended to correlate inversely with the z-scores of birth weight for gestational age (BWGA) and placental weight for gestational age (PWGA) in the second trimester, but not in the third trimester. EV-miR-26b-5p levels were positively associated with birth weight in the second trimester, but this association was weakened in the third trimester. CONCLUSION: Our results suggest a trimester-specific association of circulating miRNA levels with fetal and placental growth. The precise roles of EV-miR-127-3p and EV-miR-26b-5p in fetal and placental development warrant further investigation.

IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism.

Interleukin (IL)-19, a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. Nonalcoholic steatohepatitis (NASH) is a disease that has progressed from nonalcoholic fatty liver disease (NAFLD) and is characterized by inflammation and fibrosis. We evaluated the functions of IL-19 in a NAFLD/NASH mouse model using a 60% high fat diet with 0.1% methionine, without choline, and with 2% cholesterol (CDAHFD). Wild-type (WT) and IL-19 gene-deficient (KO) mice were fed a CDAHFD or standard diet for 9 weeks. Liver injury, inflammation, and fibrosis induced by CDAHFD were significantly worse in IL-19 KO mice than in WT mice. IL-6, TNF-α, and TGF-ß were significantly higher in IL-19 KO mice than in WT mice. As a mechanism using an in vitro experiment, palmitate-induced triglyceride and cholesterol contents were decreased by the addition of IL-19 in HepG2 cells. Furthermore, addition of IL-19 decreased the expression of fatty acid synthesis-related enzymes and increased ATP content in HepG2 cells. The action of IL-19 in vitro suppressed lipid metabolism. In conclusion, IL-19 may play an important role in the development of steatosis and fibrosis by directly regulating liver metabolism and may be a potential target for the treatment of liver diseases.

Placenta mediates the effect of maternal hypertension polygenic score on offspring birth weight: a study of birth cohort with fetal growth velocity data.

BACKGROUND: Low birth weight (LBW) and fetal growth restriction are associated with the development of cardio-metabolic diseases later in life. A recent Mendelian randomization study concluded that the susceptibility of LBW infants to develop hypertension during adulthood is due to the inheritance of hypertension genes from the mother and not to an unfavorable intrauterine environment. Therein, a negative linear association has been assumed between genetically estimated maternal blood pressure (BP) and birth weight, while the observed relationship between maternal BP and birth weight is substantially different from that assumption. As many hypertension genes are likely involved in vasculature development and function, we hypothesized that BP-increasing genetic variants could affect birth weight by reducing the growth of the placenta, a highly vascular organ, without overtly elevating the maternal BP. METHODS: Using a birth cohort in the Japanese population possessing time-series fetal growth velocity data as a target and a GWAS summary statistics of BioBank Japan as a base data, we performed polygenic score (PGS) analyses for systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure. A causal mediation analysis was performed to assess the meditation effect of placental weight on birth weight reduced by maternal BP-increasing PGS. Maternal genetic risk score constituted of only "vasculature-related" BP single nucleotide polymorphisms (SNPs) was constructed to examine the involvement of vascular genes in the mediation effect of placental weight. We identified gestational week in which maternal SBP-increasing PGS significantly decreased fetal growth velocity. RESULTS: We observed that maternal SBP-increasing PGS was negatively associated with offspring birth weight. A causal mediation analysis revealed that a large proportion of the total maternal PGS effect on birth weight was mediated by placental weight. The placental mediation effect was remarkable when genetic risk score was constituted of "vasculature-related" BP SNPs. The inverse association between maternal SBP PGS and fetal growth velocity only became apparent in late gestation. CONCLUSIONS: Our study suggests that maternal hypertension genes are strongly associated with placental growth and that fetal growth inhibition is induced through the intrauterine environment established by the placenta.

Application of the Nutrient-Rich Food Index 9.3 and the Dietary Inflammatory Index for Assessing Maternal Dietary Quality in Japan: A Single-Center Birth Cohort Study.

The maternal diet can potentially influence the life-course health of the child. A poor-quality maternal diet creates nutrient deficiencies and affects immune-metabolic regulation during pregnancy. The nutrient-based overall dietary quality can be assessed using the Nutrient-Rich Food Index 9.3 (NRF9.3), which measures adherence to the national reference daily values of nutrient intake. Pro- and anti-inflammatory nutrient intake can be assessed using the energy-adjusted dietary inflammatory index (E-DII), a comprehensive index of diet-derived inflammatory capacity. Using these indices, we assessed the overall dietary quality and inflammatory potential of pregnant women during mid-gestation in an urban area of Japan (n = 108) and found that there was a strong inverse correlation between the NRF9.3 and E-DII scores. Comparison of the scores among the tertiles of NRF9.3 or E-DII indicated that dietary fiber, vitamin C, vitamin A, and magnesium mainly contributed to the variability of both indices. Intake of vegetables and fruits was positively associated with high NRF9.3 scores and negatively associated with high E-DII scores, after adjustment for maternal age, pre-pregnancy body mass index, and educational level. Consistent with the previous studies that used dietary pattern analysis, this study also demonstrated that vegetables and fruits were the food groups chiefly associated with high dietary quality and low inflammatory potential among pregnant Japanese women.

Fucoxanthin Ameliorates Atopic Dermatitis Symptoms by Regulating Keratinocytes and Regulatory Innate Lymphoid Cells.

Fucoxanthin (FX) is a xanthophyll that is contained abundantly in marine plants. The biological action of FX includes its antioxidant and anti-lipogenic activities, while the precise action of its mechanisms on skin cells has not yet been clarified. The current study examined the effect of FX in comparison with tacrolimus (TAC) on NC/Nga mice, which are an atopic dermatitis (AD) model. FX topical treatment dramatically ameliorated itching behavior over the TAC treatment, which was insufficient for improvement of AD symptoms. In Nc/Nga mice, FX or TAC applied to the skin inhibited eosinophil infiltration with decreased expression of Il-33. FX also stimulated Il-2, Il-5, Il-13, Il-10, and TGF-ß expression levels, and Sca1+Il-10+TGF-ß+ regulatory innate lymphoid cells (ILCreg) were dominantly observed in FX treated skin epidermal keratinocytes and dermal layers. This combined evidence demonstrated that FX exerts anti-inflammatory effects on keratinocytes and ameliorates AD symptoms by regulating ILCreg to normalize immune responses in an atopic dermatitis model.

Does physical activity attenuate the association between birth weight and glycated hemoglobin in nondiabetic Japanese women?

Lower birth weight is associated with a risk of type 2 diabetes in adulthood. However, it is not clear whether this association is modified by physical activity. This study aimed to examine the association between birth weight and glycemic status and whether this association is mediated by moderate- and vigorous-intensity activity (MVPA) in Japanese women. The participants were 103 nondiabetic women (47.4 ± 10.8 years), who underwent health checkups in which data of glycated hemoglobin (HbA1c) were collected. Abdominal circumference (AC) was measured at the umbilical region. Birth weight was obtained from the Maternal and Child Health Handbook records or reported based on the participant's or his/her mother's recall. Time (min/day) spent in MVPA (≥3.0 metabolic equivalents) was objectively measured using a triaxial accelerometer (Actimarker EW4800). Birth weight was inversely correlated with HbA1c (r = -0.32, P < 0.01). Multiple linear regression analyses revealed that lower birth weight was associated with increased HbA1c (ß = -0.22, P < 0.05) even after adjusting for age, state of menstruation, AC, and family history of diabetes. This association was little changed when MVPA was introduced as an independent variable in the model (ß = -0.23, P < 0.05). These results suggest that lower birth weight may be associated with higher HbA1c levels before the onset of type 2 diabetes, irrespective of adulthood physical activity. Early-life development should be taken into account when considering the risk of diabetes in Japanese women, even if they are physically active.

Validity of estimating physical activity intensity using a triaxial accelerometer in healthy adults and older adults.

BACKGROUND: A triaxial accelerometer with an algorithm that could discriminate locomotive and non-locomotive activities in adults has been developed. However, in the elderly, this accelerometer has not yet been validated. The aim were to examine the validity of this accelerometer in the healthy elderly, and to compare the results with those derived in a healthy younger sample. METHODS: Twenty-nine healthy elderly subjects aged 60-80 years (Elderly), and 42 adults aged 20-59 years (Younger) participated. All subjects performed 11 activities, including locomotive and non-locomotive activities with a Douglas bag while wearing the accelerometer (Active style Pro HJA-750C). Physical activity intensities were expressed as metabolic equivalents (METs). The relationship between the METs measured using the Douglas bag and METs predicted using the accelerometer was evaluated. RESULTS: A significant correlation between actual and predicted METs was observed in both Elderly (r=0.85, p<0.001) and Younger (r=0.88, p<0.001). Predicted METs significantly underestimated compared with actual METs in both groups (p<0.001). The mean of the errors was -0.6±0.6 METs in Elderly and -0.1±0.5 METs in Younger. The degree of underestimation increased with increasing METs in Elderly (p<0.001). A stepwise multiple regression analysis revealed that predicted METs, age, and weight were related to actual METs in both groups. CONCLUSION: The degree of correlation between predicted and actual METs was comparable in elderly and younger participants, but the prediction errors were greater in elderly participants, particular at higher-intensity activities, which suggests that different predicting equations may be needed for the elderly.

Metabolic and Immunological Shifts during Mid-to-Late Gestation Influence Maternal Blood Methylation of CPT1A and SREBF1.

Mid-to-late gestation is a unique period in which women experience dynamic changes in lipid metabolism. Although the recent intensive epigenome-wide association studies (EWAS) using peripheral leukocytes have revealed that lipid-related traits alter DNA methylation, the influence of pregnancy-induced metabolic changes on the methylation levels of these differentially methylated sites is not well known. In this study, we performed a prospective cohort study of pregnant women (n = 52) using the MassARRAY EpiTYPER assay and analyzed the methylation levels of variably methylated sites, including CPT1A intron 1 and SREBF1 intron 1 CpGs, which were previously verified to be robustly associated with adiposity traits. Although methylation of SREBF1 was associated with body mass index (BMI) and low-density lipoprotein cholesterol at mid-gestation, this association was attenuated at late gestation, which was consistent with the metabolic switch from an anabolic to a catabolic state. However, the BMI association with CPT1A intron 1 methylation appeared to strengthen at late gestation; this association was mediated by pre-pregnancy BMI-dependent change in the leukocyte proportion during mid-to-late gestation. Thus, the methylation of adiposity-related differentially methylated regions was sensitive to metabolic and immunological changes during mid-to-late gestation.