期刊名称：Journal of Nutritional Science and Vitaminology
印刷版ISSN：0301-4800
电子版ISSN：1881-7742
出版年度：2015
卷号：61
期号：Supplement
页码：S81-S81
DOI：10.3177/jnsv.61.S81
出版社：Center for Academic Publications Japan
摘要：Nutritional condition in the fetus and neonate might affect the susceptibility to adult-onset lifestyle disease, such as obesity and type 2 diabetes. DNA methylation of the gene promoter region is a major epigenetic modification for gene expression, which can be affected by environmental factors. In the neonatal liver, fatty acid β-oxidation progressively increases to produce energy from the absorbed milk lipids. Here we show that upon the onset of breast feeding, DNA demethylation and increased mRNA expression of the fatty acid β-oxidation genes occur in the postnatal mouse liver. We also demonstrate that maternal administration of a nuclear receptor peroxisome proliferator-activated receptor (PPAR), α synthetic ligand; Wy14643 induces DNA demethylation of fatty acid β-oxidation-related genes in the liver of the offspring. Analysis of mice deficient in PPARα and maternal administration of Wy14643 during the gestation and lactation periods reveals that the DNA demethylation is PPARα-dependent. Furthermore, we find that the maternal administration of Wy14643 also results in increased DNA demethylation and mRNA expression of the gene encoding Fibroblast Growth Factor (FGF) 21, a major target gene of PPARα, in the neonatal mouse liver. Notably, the DNA methylation status and increased mRNA expression are maintained at least up to 10 wk after birth, which may be referred to as “epigenetic memory”. This study represents the first demonstration that the ligand-activated PPARα-dependent DNA demethylation regulates hepatic lipid metabolism during the neonatal period, thereby highlighting the role of a lipid-sensing nuclear receptor in the gene- and life stage-specific DNA demethylation of a particular metabolic pathway. Our data also suggest that the nutritional status in early life affects hepatic lipid metabolism in later life and thus provide clues to the “preemptive medicine” for adult-onset metabolic diseases in early life in the form of formula milk and functional food for both babies and mothers.
