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.


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*


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