Fructose consumption induces hypomethylation of hepatic mitochondrial DNA in rats

Mirai Yamazaki, Eiji Munetsuna, Hiroya Yamada, Yoshitaka Ando, Genki Mizuno, Yuri Murase, Kanako Kondo, Hiroaki Ishikawa, Ryoji Teradaira, Koji Suzuki, Koji Ohashi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Aims Fructose may play a crucial role in the pathogenesis of metabolic syndrome (MetS). However, the pathogenic mechanism of the fructose-induced MetS has not yet been investigated fully. Recently, several reports have investigated the association between mitochondrial DNA (mtDNA) and MetS. We examined the effect of fructose-rich diets on mtDNA content, transcription, and epigenetic changes. Main methods Four-week-old male Sprague-Dawley rats were offered a 20% fructose solution for 14 weeks. We quantified mRNAs for hepatic mitochondrial genes and analyzed the mtDNA methylation (5-mC and 5-hmC) levels using ELISA kits. Key findings Histological analysis revealed non-alcoholic fatty liver disease (NAFLD) in fructose-fed rats. Hepatic mtDNA content and transcription were higher in fructose-fed rats than in the control group. Global hypomethylation of mtDNA was also observed in fructose-fed rats. Significance We showed that fructose consumption stimulates hepatic mtDNA-encoded gene expression. This phenomenon might be due to epigenetic changes in mtDNA. Fructose-induced mitochondrial epigenetic changes appear to be a novel mechanism underlying the pathology of MetS and NAFLD.

Original languageEnglish
Pages (from-to)146-152
Number of pages7
JournalLife Sciences
Volume149
DOIs
Publication statusPublished - 15-03-2016

Fingerprint

Fructose
Mitochondrial DNA
Rats
Liver
Epigenomics
Transcription
Mitochondrial Genes
Pathology
DNA Methylation
Nutrition
Gene expression
Sprague Dawley Rats
Genes
Enzyme-Linked Immunosorbent Assay
Diet
Gene Expression
Control Groups
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Yamazaki, Mirai ; Munetsuna, Eiji ; Yamada, Hiroya ; Ando, Yoshitaka ; Mizuno, Genki ; Murase, Yuri ; Kondo, Kanako ; Ishikawa, Hiroaki ; Teradaira, Ryoji ; Suzuki, Koji ; Ohashi, Koji. / Fructose consumption induces hypomethylation of hepatic mitochondrial DNA in rats. In: Life Sciences. 2016 ; Vol. 149. pp. 146-152.
@article{78cffe4a51434896b623f4ca26a916ab,
title = "Fructose consumption induces hypomethylation of hepatic mitochondrial DNA in rats",
abstract = "Aims Fructose may play a crucial role in the pathogenesis of metabolic syndrome (MetS). However, the pathogenic mechanism of the fructose-induced MetS has not yet been investigated fully. Recently, several reports have investigated the association between mitochondrial DNA (mtDNA) and MetS. We examined the effect of fructose-rich diets on mtDNA content, transcription, and epigenetic changes. Main methods Four-week-old male Sprague-Dawley rats were offered a 20{\%} fructose solution for 14 weeks. We quantified mRNAs for hepatic mitochondrial genes and analyzed the mtDNA methylation (5-mC and 5-hmC) levels using ELISA kits. Key findings Histological analysis revealed non-alcoholic fatty liver disease (NAFLD) in fructose-fed rats. Hepatic mtDNA content and transcription were higher in fructose-fed rats than in the control group. Global hypomethylation of mtDNA was also observed in fructose-fed rats. Significance We showed that fructose consumption stimulates hepatic mtDNA-encoded gene expression. This phenomenon might be due to epigenetic changes in mtDNA. Fructose-induced mitochondrial epigenetic changes appear to be a novel mechanism underlying the pathology of MetS and NAFLD.",
author = "Mirai Yamazaki and Eiji Munetsuna and Hiroya Yamada and Yoshitaka Ando and Genki Mizuno and Yuri Murase and Kanako Kondo and Hiroaki Ishikawa and Ryoji Teradaira and Koji Suzuki and Koji Ohashi",
year = "2016",
month = "3",
day = "15",
doi = "10.1016/j.lfs.2016.02.020",
language = "English",
volume = "149",
pages = "146--152",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",

}

Fructose consumption induces hypomethylation of hepatic mitochondrial DNA in rats. / Yamazaki, Mirai; Munetsuna, Eiji; Yamada, Hiroya; Ando, Yoshitaka; Mizuno, Genki; Murase, Yuri; Kondo, Kanako; Ishikawa, Hiroaki; Teradaira, Ryoji; Suzuki, Koji; Ohashi, Koji.

In: Life Sciences, Vol. 149, 15.03.2016, p. 146-152.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Fructose consumption induces hypomethylation of hepatic mitochondrial DNA in rats

AU - Yamazaki, Mirai

AU - Munetsuna, Eiji

AU - Yamada, Hiroya

AU - Ando, Yoshitaka

AU - Mizuno, Genki

AU - Murase, Yuri

AU - Kondo, Kanako

AU - Ishikawa, Hiroaki

AU - Teradaira, Ryoji

AU - Suzuki, Koji

AU - Ohashi, Koji

PY - 2016/3/15

Y1 - 2016/3/15

N2 - Aims Fructose may play a crucial role in the pathogenesis of metabolic syndrome (MetS). However, the pathogenic mechanism of the fructose-induced MetS has not yet been investigated fully. Recently, several reports have investigated the association between mitochondrial DNA (mtDNA) and MetS. We examined the effect of fructose-rich diets on mtDNA content, transcription, and epigenetic changes. Main methods Four-week-old male Sprague-Dawley rats were offered a 20% fructose solution for 14 weeks. We quantified mRNAs for hepatic mitochondrial genes and analyzed the mtDNA methylation (5-mC and 5-hmC) levels using ELISA kits. Key findings Histological analysis revealed non-alcoholic fatty liver disease (NAFLD) in fructose-fed rats. Hepatic mtDNA content and transcription were higher in fructose-fed rats than in the control group. Global hypomethylation of mtDNA was also observed in fructose-fed rats. Significance We showed that fructose consumption stimulates hepatic mtDNA-encoded gene expression. This phenomenon might be due to epigenetic changes in mtDNA. Fructose-induced mitochondrial epigenetic changes appear to be a novel mechanism underlying the pathology of MetS and NAFLD.

AB - Aims Fructose may play a crucial role in the pathogenesis of metabolic syndrome (MetS). However, the pathogenic mechanism of the fructose-induced MetS has not yet been investigated fully. Recently, several reports have investigated the association between mitochondrial DNA (mtDNA) and MetS. We examined the effect of fructose-rich diets on mtDNA content, transcription, and epigenetic changes. Main methods Four-week-old male Sprague-Dawley rats were offered a 20% fructose solution for 14 weeks. We quantified mRNAs for hepatic mitochondrial genes and analyzed the mtDNA methylation (5-mC and 5-hmC) levels using ELISA kits. Key findings Histological analysis revealed non-alcoholic fatty liver disease (NAFLD) in fructose-fed rats. Hepatic mtDNA content and transcription were higher in fructose-fed rats than in the control group. Global hypomethylation of mtDNA was also observed in fructose-fed rats. Significance We showed that fructose consumption stimulates hepatic mtDNA-encoded gene expression. This phenomenon might be due to epigenetic changes in mtDNA. Fructose-induced mitochondrial epigenetic changes appear to be a novel mechanism underlying the pathology of MetS and NAFLD.

UR - http://www.scopus.com/inward/record.url?scp=84959422206&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959422206&partnerID=8YFLogxK

U2 - 10.1016/j.lfs.2016.02.020

DO - 10.1016/j.lfs.2016.02.020

M3 - Article

C2 - 26869391

AN - SCOPUS:84959422206

VL - 149

SP - 146

EP - 152

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

ER -