Epigenetic switching and neonatal nutritional environment

Koshi Hashimoto, Yoshihiro Ogawa

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Citations (Scopus)


The hepatic metabolic function changes sequentially during early life in mammals to adapt to the drastic changes in the nutritional environment. Accordingly, hepatic fatty acid β-oxidation is activated after birth to produce energy from breast milk lipids. De novo lipogenesis is induced upon the onset of oral intake, when the major nutritional source switches to carbohydrate. However, how a particular metabolic pathway is activated during the liver maturation is poorly understood. We found that the expression of glycerol-3-phosphate acyltransferase 1 (GPAT1), a rate-limiting enzyme of de novo hepatic lipogenesis, is epigenetically regulated in the mouse liver by DNA methylation. In the neonatal liver, DNA methylation of the GPAT1 gene (Gpam) promoter, which is likely to be induced by DNA methyltransferase (Dnmt) 3b, inhibited the recruitment of sterol regulatory element-binding protein-1c (SREBP-1c), whereas in the adult, decreased DNA methylation resulted in active chromatin conformation, allowing the recruitment of SREBP-1c. Maternal nutritional environment affects the DNA methylation status in the Gpam promoter, GPAT1 expression, and triglyceride content in the liver of the offspring. We also found DNA demethylation and increased mRNA expression of the fatty acid β-oxidation genes in the postnatal mouse liver. The DNA demethylation is specifically induced in the lactation period. Analysis of mice deficient in the nuclear receptor peroxisome proliferator-activated receptor α (PPARα) and maternal administration of a PPARα ligand during the gestation and lactation periods reveals that the DNA demethylation is PPARα-dependent. These findings indicate the gene- and lifestage-specific DNA demethylation of a particular metabolic pathway in the neonatal liver to adapt the marked changes in nutritional environment in early life.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Number of pages7
Publication statusPublished - 2018

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


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