Epigenetic switching and neonatal nutritional environment

Koshi Hashimoto, Yoshihiro Ogawa

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Citations (Scopus)

Abstract

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
Pages19-25
Number of pages7
DOIs
Publication statusPublished - Jan 1 2018

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1012
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Fingerprint

Epigenomics
Liver
Acyltransferases
Peroxisome Proliferator-Activated Receptors
DNA Methylation
Sterol Regulatory Element Binding Protein 1
Genes
DNA
Lipogenesis
Fatty Acids
Metabolic Networks and Pathways
Lactation
Oxidation
Mammals
Cytoplasmic and Nuclear Receptors
Mothers
Chromatin
Conformations
Triglycerides
Switches

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hashimoto, K., & Ogawa, Y. (2018). Epigenetic switching and neonatal nutritional environment. In Advances in Experimental Medicine and Biology (pp. 19-25). (Advances in Experimental Medicine and Biology; Vol. 1012). Springer New York LLC. https://doi.org/10.1007/978-981-10-5526-3_3

Epigenetic switching and neonatal nutritional environment. / Hashimoto, Koshi; Ogawa, Yoshihiro.

Advances in Experimental Medicine and Biology. Springer New York LLC, 2018. p. 19-25 (Advances in Experimental Medicine and Biology; Vol. 1012).

Research output: Chapter in Book/Report/Conference proceedingChapter

Hashimoto, K & Ogawa, Y 2018, Epigenetic switching and neonatal nutritional environment. in Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology, vol. 1012, Springer New York LLC, pp. 19-25. https://doi.org/10.1007/978-981-10-5526-3_3
Hashimoto K, Ogawa Y. Epigenetic switching and neonatal nutritional environment. In Advances in Experimental Medicine and Biology. Springer New York LLC. 2018. p. 19-25. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-981-10-5526-3_3
Hashimoto, Koshi ; Ogawa, Yoshihiro. / Epigenetic switching and neonatal nutritional environment. Advances in Experimental Medicine and Biology. Springer New York LLC, 2018. pp. 19-25 (Advances in Experimental Medicine and Biology).
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