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

International Journal of Molecular Sciences

Motoko Okamitsu¹  Satoshi Yago¹  Naoyuki Miyasaka²  Ayako Fudono²  Xin Jin³  Noriko Sato³  Chihiro Imai³  Naomi Hichiwa³  Masaaki Muramatsu³  Shilpa Pavethynath³  Tomoko Aoyama⁴  Iori Tarui⁴  Hidemi Takimoto⁴ 

[1] Child and Family Nursing, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan;Comprehensive Reproductive Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan;Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan;Department of Nutritional Epidemiology, National Institute of Health and Nutrition, Tokyo 162-8636, Japan;

关键词: pregnancy;    DNA methylation;    CPT1A;    SREBF1;    leukocyte composition;   

DOI  :  10.3390/ijms20051066

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown