{"title":"Approaches to nutritional research using organoids; fructose treatment induces epigenetic changes in liver organoids","authors":"Mirai Yamazaki , Hiroya Yamada , Eiji Munetsuna , Yoshitaka Ando , Genki Mizuno , Atsushi Teshigawara , Hayato Ichikawa , Yuki Nouchi , Itsuki Kageyama , Takuya Wakasugi , Hiroaki Ishikawa , Nobutaka Ohgami , Koji Suzuki , Koji Ohashi","doi":"10.1016/j.jnutbio.2024.109671","DOIUrl":null,"url":null,"abstract":"<div><p>Nutritional researches have successfully used animal models to gain new insights into nutrient action. However, comprehensive descriptions of their molecular mechanisms of action remain elusive as appropriate <em>in vitro</em> evaluation systems are lacking. Organoid models can mimic physiological structures and reproduce <em>in vivo</em> functions, making them increasingly utilized in biomedical research for a better understand physiological and pathological phenomena. Therefore, organoid modeling can be a powerful approach for to understand the molecular mechanisms of nutrient action. The present study aims to demonstrate the utility of organoids in nutritional research by further investigating the molecular mechanisms responsible for the negative effects of fructose intake using liver organoids. Here, we treated liver organoids with fructose and analyzed their gene expression profiles and DNA methylation levels. Microarray analysis demonstrated that fructose-treated organoids exhibited increased selenoprotein p (<em>Sepp1</em>) gene expression, whereas pyrosequencing assays revealed reduced DNA methylation levels in the <em>Sepp1</em> region. These results were consistent with observations using hepatic tissues from fructose-fed rats. Conversely, no differences in <em>Sepp1</em> mRNA and DNA methylation levels were observed in two-dimensional cells. These results suggest that organoids serve as an ideal <em>in vitro</em> model to recapitulate <em>in vivo</em> tissue responses and help to validate the molecular mechanisms of nutrient action compared to conventional cellular models.</p></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"131 ","pages":"Article 109671"},"PeriodicalIF":4.8000,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nutritional Biochemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0955286324001049","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Nutritional researches have successfully used animal models to gain new insights into nutrient action. However, comprehensive descriptions of their molecular mechanisms of action remain elusive as appropriate in vitro evaluation systems are lacking. Organoid models can mimic physiological structures and reproduce in vivo functions, making them increasingly utilized in biomedical research for a better understand physiological and pathological phenomena. Therefore, organoid modeling can be a powerful approach for to understand the molecular mechanisms of nutrient action. The present study aims to demonstrate the utility of organoids in nutritional research by further investigating the molecular mechanisms responsible for the negative effects of fructose intake using liver organoids. Here, we treated liver organoids with fructose and analyzed their gene expression profiles and DNA methylation levels. Microarray analysis demonstrated that fructose-treated organoids exhibited increased selenoprotein p (Sepp1) gene expression, whereas pyrosequencing assays revealed reduced DNA methylation levels in the Sepp1 region. These results were consistent with observations using hepatic tissues from fructose-fed rats. Conversely, no differences in Sepp1 mRNA and DNA methylation levels were observed in two-dimensional cells. These results suggest that organoids serve as an ideal in vitro model to recapitulate in vivo tissue responses and help to validate the molecular mechanisms of nutrient action compared to conventional cellular models.
期刊介绍:
Devoted to advancements in nutritional sciences, The Journal of Nutritional Biochemistry presents experimental nutrition research as it relates to: biochemistry, molecular biology, toxicology, or physiology.
Rigorous reviews by an international editorial board of distinguished scientists ensure publication of the most current and key research being conducted in nutrition at the cellular, animal and human level. In addition to its monthly features of critical reviews and research articles, The Journal of Nutritional Biochemistry also periodically publishes emerging issues, experimental methods, and other types of articles.