Fructose consumption induces hypomethylation of hepatic mitochondrial DNA in rats

M Yamazaki, E Munetsuna, H Yamada, Y Ando… - Life sciences, 2016 - Elsevier
M Yamazaki, E Munetsuna, H Yamada, Y Ando, G Mizuno, Y Murase, K Kondo, H Ishikawa…
Life sciences, 2016Elsevier
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 …
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.
Elsevier