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

Abstract

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.

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 current research was based on a prospective mother-child cohort study in the Metropolitan Tokyo area: the Birth Cohort Gene and ENvironment Interaction Study of Tokyo Medical and Dental University (TMDU) (BC-GENIST), which was designed to evaluate the effects of the prenatal environment and genotype on the epigenetic state of mothers and their offspring [ 32 ]. During the years 2015–2019, pregnant women in their first trimester were recruited to BC-GENIST at the TMDU hospital ( n = 126).…”

Differential DNA methylation profile in infants born small-for-gestational-age: association with markers of adiposity and insulin resistance from birth to age 24 months

“… 40 Recently, epigenome-wide association studies have disclosed the causal role of CPT1A methylation in type 2 diabetes 41 and the association between intron 1 CPT1A methylation and gestational BMI. 42 …”

Nuclear Factor Erythroid 2 Related Factor 2 Activator JC-5411 Inhibits Atherosclerosis Through Suppression of Inflammation and Regulation of Lipid Metabolism

“…The results showed that JC-5411 treatment significantly increased the protein expression levels of ABCA1 and LDLR in the livers of ApoE −/− mice when compared with model group (Figures 5C, D). Moreover, JC-5411 treatment decreased the protein level of SCD1 (an enzyme that catalyzes the synthesis of fatty acids (ALJohani et al, 2017)), but increased the inactivation form of the rate-limiting enzyme of de novo fatty acid synthesis p-ACC (Kim et al, 2017) and the fatty acid β-oxidation CPT1A (Pavethynath et al, 2019) protein levels when compared with model group (Figures 5C, D). What's more, JC-5411 treatment also decreased the protein level of fatty acid synthase (FAS), one of the important lipogenic genes (Wang and Tontonoz, 2018), but did not affect the protein level of sterol regulatory elementbinding protein 1 (SREBP-1), peroxisome proliferatoractivated receptor α (PPARα) and Liver X receptors α (LXRα) ( Figures 5C, D).…”