Plasticity of histone modifications around Cidea and Cidec genes with secondary bile in the amelioration of developmentally-programmed hepatic steatosis

Jeenat Ferdous Urmi; Hiroaki Itoh; Keiko Muramatsu-Kato; Yukiko Kohmura-Kobayashi; Natsuyo Hariya; Divyanu Jain; Naoaki Tamura; Toshiyuki Uchida; Kazunao Suzuki; Yoshihiro Ogawa; Nobuaki Shiraki; Kazuki Mochizuki; Takeo Kubota; Naohiro Kanayama

doi:10.1038/s41598-019-52943-7

Plasticity of histone modifications around Cidea and Cidec genes with secondary bile in the amelioration of developmentally-programmed hepatic steatosis

Sci Rep. 2019 Nov 19;9(1):17100. doi: 10.1038/s41598-019-52943-7.

Authors

Affiliations

¹ Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
² Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Japan. hitou-endo@umin.ac.jp.
³ Department of Nutrition, Faculty of Health and Nutrition, Sciences, Yamanashi Gakuin University, Yamanashi, Japan.
⁴ Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁵ Department of Molecular and Cellular Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
⁶ Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan.
⁷ Laboratory of Food and Nutritional Sciences, Department of Local Produce and Food Sciences, Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi, Japan.
⁸ Faculty of Child Studies, Seitoku University, Matsudo, Japan.

Abstract

We recently reported that a treatment with tauroursodeoxycholic acid (TUDCA), a secondary bile acid, improved developmentally-deteriorated hepatic steatosis in an undernourishment (UN, 40% caloric restriction) in utero mouse model after a postnatal high-fat diet (HFD). We performed a microarray analysis and focused on two genes (Cidea and Cidec) because they are enhancers of lipid droplet (LD) sizes in hepatocytes and showed the greatest up-regulation in expression by UN that were completely recovered by TUDCA, concomitant with parallel changes in LD sizes. TUDCA remodeled developmentally-induced histone modifications (dimethylation of H3K4, H3K27, or H3K36), but not DNA methylation, around the Cidea and Cidec genes in UN pups only. Changes in these histone modifications may contribute to the markedly down-regulated expression of Cidea and Cidec genes in UN pups, which was observed in the alleviation of hepatic fat deposition, even under HFD. These results provide an insight into the future of precision medicine for developmentally-programmed hepatic steatosis by targeting histone modifications.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis Regulatory Proteins / genetics*
Cholagogues and Choleretics / pharmacology
Diet, High-Fat / adverse effects
Fatty Liver / drug therapy
Fatty Liver / etiology
Fatty Liver / genetics*
Gene Expression Profiling
Gene Expression Regulation, Developmental / drug effects*
Histone Code / drug effects*
Male
Mice
Mice, Inbred C57BL
Protein Processing, Post-Translational*
Proteins / genetics*
Taurochenodeoxycholic Acid / pharmacology*

Substances

Apoptosis Regulatory Proteins
Cholagogues and Choleretics
Cidea protein, mouse
Proteins
fat-specific protein 27, mouse
Taurochenodeoxycholic Acid
ursodoxicoltaurine