Dataset Information

Maternal Glucose and LDL-Cholesterol Levels Are Related to Placental Leptin Gene Methylation, and, Together With Nutritional Factors, Largely Explain a Higher Methylation Level Among Ethnic South Asians.

ABSTRACT:

Background

Leptin, mainly secreted by fat cells, plays a core role in the regulation of appetite and body weight, and has been proposed as a mediator of metabolic programming. During pregnancy leptin is also secreted by the placenta, as well as being a key regulatory cytokine for the development, homeostatic regulation and nutrient transport within the placenta. South Asians have a high burden of type 2 diabetes, partly attributed to a "thin-fat-phenotype".

Objective

Our aim was to investigate how maternal ethnicity, adiposity and glucose- and lipid/cholesterol levels in pregnancy are related to placental leptin gene (LEP) DNA methylation.

Methods

We performed DNA methylation analyses of 13 placental LEP CpG sites in 40 ethnic Europeans and 40 ethnic South Asians participating in the STORK-Groruddalen cohort.

Results

South Asian ethnicity and gestational diabetes (GDM) were associated with higher placental LEP methylation. The largest ethnic difference was found for CpG11 [5.8% (95% CI: 2.4, 9.2), p<0.001], and the strongest associations with GDM was seen for CpG5 [5.2% (1.4, 9.0), p=0.008]. Higher maternal LDL-cholesterol was associated with lower placental LEP methylation, in particular for CpG11 [-3.6% (-5.5, -1.4) per one mmol/L increase in LDL, p<0.001]. After adjustments, including for nutritional factors involved in the one-carbon-metabolism cycle (vitamin D, B12 and folate levels), ethnic differences in placental LEP methylation were strongly attenuated, while associations with glucose and LDL-cholesterol persisted.

Conclusions

Maternal glucose and lipid metabolism is related to placental LEP methylation, whilst metabolic and nutritional factors largely explain a higher methylation level among ethnic South Asians.

SUBMITTER: Sletner L

PROVIDER: S-EPMC8739998 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Diets higher in plants are associated with lower risks of chronic diseases. However, animal foods, which are rich in protein, are also rich in some important minerals and vitamins. Using data from a representative survey in France (INCA3, n = 1,125), we used path analyses as a mediation-like approach to decipher the importance of plant and animal proteins in the relationship between the plant-based diet index (PDI) and diet quality. We used three types of diet quality scores, namely, nutrient security, positive nutrient adequacy, and long-term mortality risk of four diet-related diseases (i.e., coronary heart disease, stroke, type 2 diabetes, and colorectal cancer). We identified positive and negative mediations, i.e., changes in plant/animal protein intake that are associated with changes in PDI, and favor or limit the association with the diet quality score. The PDI was positively associated with the risk of long-term mortality but not significantly with nutrient adequacy or nutrient security. A positive mediation by plant protein was found for all diet quality scores (specific indirect effects (SIEs) ranging from 0.04 to 0.10 SD). Conversely, the association between PDI and nutrient adequacy (but not nutrient security) was negatively mediated by animal protein intake (SIE: -0.06 SD). In further detailed models, the association between PDI and diet quality was mainly positively mediated by protein foods from the fruit-vegetables-legumes group (0.01 SD for the nutrient security and 0.02 SD for the nutrient adequacy) and whole grains (0.02 SD for the nutrient adequacy). Our data suggest that the positive impact of plant-based diets on diet quality is largely driven by higher intakes of plant protein foods, especially from fruits-vegetables-legumes and whole grains. Conversely, lower animal protein intake tends to limit the positive impact of plant-based diets on overall positive nutrient adequacy but not security. Protein sources appear critical to healthy plant-based diets.

Project description:BackgroundParticulate matter with a diameter ≤ 2.5 μm (PM2.5) affects human fetal development during pregnancy. Oxidative stress is a putative mechanism by which PM2.5 may exert its effects. Leptin (LEP) is an energy-regulating hormone involved in fetal growth and development.ObjectivesWe investigated in placental tissue whether DNA methylation of the LEP promoter is associated with PM2.5 and whether the oxidative/nitrosative stress biomarker 3-nitrotyrosine (3-NTp) is involved.MethodsLEP DNA methylation status of 361 placentas from the ENVIRONAGE birth cohort was assessed using bisulfite-PCR-pyrosequencing. Placental 3-NTp (n = 313) was determined with an ELISA assay. Daily PM2.5 exposure levels were estimated for each mother's residence, accounting for residential mobility during pregnancy, using a spatiotemporal interpolation model.ResultsAfter adjustment for a priori chosen covariates, placental LEP methylation was 1.4% lower (95% CI: -2.7, -0.19%) in association with an interquartile range increment (7.5 μg/m3) in second-trimester PM2.5 exposure and 0.43% lower (95% CI: -0.85, -0.02%) in association with a doubling of placental 3-NTp content.ConclusionsLEP methylation status in the placenta was negatively associated with PM2.5 exposure during the second trimester, and with placental 3-NTp, a marker of oxidative/nitrosative stress. Additional research is needed to confirm our findings and to assess whether oxidative/nitrosative stress might contribute to associations between PM2.5 and placental epigenetic events. Potential consequences for health during the neonatal period and later in life warrant further exploration. Citation: Saenen ND, Vrijens K, Janssen BG, Roels HA, Neven KY, Vanden Berghe W, Gyselaers W, Vanpoucke C, Lefebvre W, De Boever P, Nawrot TS. 2017. Lower placental leptin promoter methylation in association with fine particulate matter air pollution during pregnancy and placental nitrosative stress at birth in the ENVIRONAGE cohort. Environ Health Perspect 125:262-268; http://dx.doi.org/10.1289/EHP38.