One-Carbon Metabolism and Lipid Metabolism in DOHaD
The predisposing factors to lifestyle-associated diseases are established in the early period of life with underlying gene-environment interaction. Epigenetics is a chemical modification-based genetic mechanism that is affected by various nutritional fact
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The predisposing factors to lifestyle- associated diseases are established in the early period of life with underlying gene- environment interaction. Epigenetics is a chemical modification-based genetic mechanism that is affected by various nutritional factors. One-carbon metabolism is a metabolic system associated with methyl residue that is supplied from folic acid. Therefore, from the epigenetic point of view, proper intake of folic acid is important for pregnant women not only to prevent congenital abnormalities such as neural tube defect but also to prevent various adult disorders of the offspring. Dyslipidemia is an important risk factor of coronary heart disease, and epidemiological studies on Dutch winter famine, Jewish holocaust survivors, and Chinese famine suggested that prenatal malnutrition was associated with the dyslipidemia. Recent animal studies revealed that malnutrition in utero causes an epigenetic change in the Pparα gene, which accelerates the activity of delta-6 desaturase and delta-5 1 H. Fukuoka (*) Research Organization for Nano & Life Innovation, Waseda University, Tokyo, Japan e-mail: [email protected] T. Kubota Faculty of Child Studies, Seitoku University, Matsudo, Chiba, Japan
desaturase, that potentially induces dyslipidemia in adulthood. It has been known that overnutrition also increased the risk of cardiovascular diseases. Recent animal studies revealed that high-fat diet increased DNA methylation in the promoter region of delta-6 desaturase gene (Fads 2) that downregulates the gene expression in the arterial smooth muscle, which potentially contributes to cardiovascular diseases. Taken together, either insufficient or excessive nutrition alters epigenetic modification of genes that encodes enzymes associated with lipid metabolism. This altered epigenetic state persists during one’s lifetime, which is potentially involved in noncommunicable diseases in adulthood. Keywords
One-carbon metabolism · Lipid metabolism · DOHaD · Epigenetics · Fads 2
Introduction
A number of epidemiological studies provided evidence that support the concept of developmental origins of health and disease (DOHaD). Recent animal studies revealed that malnutrition affects epigenetic modifications, and this is a potential molecular mechanism for DOHaD. These diseases are caused via the two stages, first and sec-
© Springer Nature Singapore Pte Ltd. 2018 T. Kubota, H. Fukuoka (eds.), Developmental Origins of Health and Disease (DOHaD), Advances in Experimental Medicine and Biology 1012, https://doi.org/10.1007/978-981-10-5526-3_1
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H. Fukuoka and T. Kubota
4 Fig. 1 One-carbon metabolism
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ond insults. The predisposing factors to lifestyle-associated diseases are established in the early period of life, such as periconceptional, embryonic, fetal, and neonatal periods with underlying gene-environment interaction (first insul
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