High-fat diet in early life triggers both reversible and persistent epigenetic changes in the medaka fish (Oryzias latipes)

BMC Genomics

Research

Terumi Washio¹  Yusuke Inoue¹  Yoshimi Kunishima¹  Hiroyuki Takeda²  Shinichi Morishita³  Yuta Suzuki³ 

[1] Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, 113-0033, Tokyo, Japan;Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, 113-0033, Tokyo, Japan;Faculty of Life Sciences, Kyoto Sangyo University, Motoyama, Kamigamo, Kita-ku, 603-8555, Kyoto, Japan;Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, 277-8561, Kashiwa, Chiba, Japan;

关键词: Nutritional programming;    High-fat diet;    Fatty liver;    Chromatin accessibility;    Histone modifications;    Medaka;   

DOI  :  10.1186/s12864-023-09557-1

 received in 2023-05-11, accepted in 2023-08-04,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe nutritional status during early life can have enduring effects on an animal’s metabolism, although the mechanisms underlying these long-term effects are still unclear. Epigenetic modifications are considered a prime candidate mechanism for encoding early-life nutritional memories during this critical developmental period. However, the extent to which these epigenetic changes occur and persist over time remains uncertain, in part due to challenges associated with directly stimulating the fetus with specific nutrients in viviparous mammalian systems.ResultsIn this study, we used medaka as an oviparous vertebrate model to establish an early-life high-fat diet (HFD) model. Larvae were fed with HFD from the hatching stages (one week after fertilization) for six weeks, followed by normal chow (NC) for eight weeks until the adult stage. We examined the changes in the transcriptomic and epigenetic state of the liver over this period. We found that HFD induces simple liver steatosis, accompanied by drastic changes in the hepatic transcriptome, chromatin accessibility, and histone modifications, especially in metabolic genes. These changes were largely reversed after the long-term NC, demonstrating the high plasticity of the epigenetic state in hepatocytes. However, we found a certain number of genomic loci showing non-reversible epigenetic changes, especially around genes related to cell signaling, liver fibrosis, and hepatocellular carcinoma, implying persistent changes in the cellular state of the liver triggered by early-life HFD feeding.ConclusionIn summary, our data show that early-life HFD feeding triggers both reversible and persistent epigenetic changes in medaka hepatocytes. Our data provide novel insights into the epigenetic mechanism of nutritional programming and a comprehensive atlas of the long-term epigenetic state in an early-life HFD model of non-mammalian vertebrates.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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