title: Fructose consumption induces hypomethylation of hepatic mitochondrial DNA in rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Four-week-old male Sprague-Dawley rats were offered a 20% fructose solution for 14weeks. We quantified mRNAs for hepatic mitochondrial genes and analyzed the mtDNA methylation (5-mC and 5-hmC) levels using ELISA kits.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors: Mirai
authors: M
authors: Yamazaki
authors: Department of Biochemistry, Fujita Health University School of Medicine, Toyoake, Japan.
authors: Eiji
authors: E
authors: Munetsuna
authors: Department of Hygiene, Fujita Health University School of Medicine, Toyoake, Japan. Electronic address: hyamada@fujita-hu.ac.jp.
authors: Hiroya
authors: H
authors: Yamada
authors: Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Toyoake, Japan.
authors: Yoshitaka
authors: Y
authors: Ando
authors: Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors: Genki
authors: G
authors: Mizuno
authors: Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors: Yuri
authors: Y
authors: Murase
authors: Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors: Kanako
authors: K
authors: Kondo
authors: Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors: Hiroaki
authors: H
authors: Ishikawa
authors: Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors: Ryoji
authors: R
authors: Teradaira
authors: Department of Public Health, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors: Koji
authors: K
authors: Suzuki
authors: Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan. Electronic address: ohashi@fujita-hu.ac.jp.
authors: Koji
authors: K
authors: Ohashi
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000187:drug effects / Q000502:physiology*; D004272:DNA, Mitochondrial / Q000378:metabolism*; D019422:Dietary Sucrose / Q000008:administration & dosage / Q000009:adverse effects; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004272:DNA, Mitochondrial; D019422:Dietary Sucrose; D005632:Fructose
keywords: 5-Hydroxymethylcytosine; 5-Methylcytosine; Fructose-induced hypomethylation; Metabolic syndrome; Non-alcoholic fatty liver disease