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Article

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

1
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
2
Department of Nutritional Epidemiology, National Institute of Health and Nutrition, Tokyo 162-8636, Japan
3
Child and Family Nursing, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
4
Comprehensive Reproductive Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
*
Author to whom correspondence should be addressed.
These authors have equally contributed to this work.
Int. J. Mol. Sci. 2019, 20(5), 1066; https://doi.org/10.3390/ijms20051066
Received: 6 February 2019 / Revised: 19 February 2019 / Accepted: 25 February 2019 / Published: 1 March 2019
(This article belongs to the Special Issue Epigenetics in Metabolic and Neurological Disorders)
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. View Full-Text
Keywords: pregnancy; DNA methylation; CPT1A; SREBF1; leukocyte composition pregnancy; DNA methylation; CPT1A; SREBF1; leukocyte composition
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MDPI and ACS Style

Pavethynath, S.; Imai, C.; Jin, X.; Hichiwa, N.; Takimoto, H.; Okamitsu, M.; Tarui, I.; Aoyama, T.; Yago, S.; Fudono, A.; Muramatsu, M.; Miyasaka, N.; Sato, N. Metabolic and Immunological Shifts during Mid-to-Late Gestation Influence Maternal Blood Methylation of CPT1A and SREBF1. Int. J. Mol. Sci. 2019, 20, 1066. https://doi.org/10.3390/ijms20051066

AMA Style

Pavethynath S, Imai C, Jin X, Hichiwa N, Takimoto H, Okamitsu M, Tarui I, Aoyama T, Yago S, Fudono A, Muramatsu M, Miyasaka N, Sato N. Metabolic and Immunological Shifts during Mid-to-Late Gestation Influence Maternal Blood Methylation of CPT1A and SREBF1. International Journal of Molecular Sciences. 2019; 20(5):1066. https://doi.org/10.3390/ijms20051066

Chicago/Turabian Style

Pavethynath, Shilpa, Chihiro Imai, Xin Jin, Naomi Hichiwa, Hidemi Takimoto, Motoko Okamitsu, Iori Tarui, Tomoko Aoyama, Satoshi Yago, Ayako Fudono, Masaaki Muramatsu, Naoyuki Miyasaka, and Noriko Sato. 2019. "Metabolic and Immunological Shifts during Mid-to-Late Gestation Influence Maternal Blood Methylation of CPT1A and SREBF1" International Journal of Molecular Sciences 20, no. 5: 1066. https://doi.org/10.3390/ijms20051066

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