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.

Details

Title
Plasticity of histone modifications around Cidea and Cidec genes with secondary bile in the amelioration of developmentally-programmed hepatic steatosis
Author
Jeenat Ferdous Urmi 1 ; Itoh, Hiroaki 1 ; Muramatsu-Kato, Keiko 1 ; Kohmura-Kobayashi, Yukiko 1 ; Hariya, Natsuyo 2 ; Jain, Divyanu 1 ; Tamura, Naoaki 1 ; Uchida, Toshiyuki 1 ; Suzuki, Kazunao 1 ; Ogawa, Yoshihiro 3 ; Shiraki, Nobuaki 4 ; Mochizuki, Kazuki 5 ; Kubota, Takeo 6 ; Kanayama, Naohiro 1 

1  Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Japan 
2  Department of Nutrition, Faculty of Health and Nutrition, Sciences, Yamanashi Gakuin University, Yamanashi, Japan 
3  Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Molecular and Cellular Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan 
4  Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan 
5  Laboratory of Food and Nutritional Sciences, Department of Local Produce and Food Sciences, Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi, Japan 
6  Faculty of Child Studies, Seitoku University, Matsudo, Japan 
Pages
1-12
Publication year
2019
Publication date
Nov 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-019-52943-7
ProQuest document ID
2315958150
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.