Mirai Yamazaki1, Eiji Munetsuna2, Hiroya Yamada3, Yoshitaka Ando4, Genki Mizuno1, Yuri Murase1, Kanako Kondo1, Hiroaki Ishikawa1, Ryoji Teradaira1, Koji Suzuki5, Koji Ohashi6. 1. Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan. 2. Department of Biochemistry, Fujita Health University School of Medicine, Toyoake, Japan. 3. Department of Hygiene, Fujita Health University School of Medicine, Toyoake, Japan. Electronic address: hyamada@fujita-hu.ac.jp. 4. Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Toyoake, Japan. 5. Department of Public Health, Fujita Health University School of Health Sciences, Toyoake, Japan. 6. Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan. Electronic address: ohashi@fujita-hu.ac.jp.
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 14weeks. 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.
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 14weeks. 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.
Authors: Antonio Anax F de Oliveira; Tiago F de Oliveira; Larissa L Bobadilla; Camila C M Garcia; Carolina Maria Berra; Nadja C de Souza-Pinto; Marisa H G Medeiros; Paolo Di Mascio; Roberto Zatz; Ana Paula de M Loureiro Journal: Sci Rep Date: 2017-01-12 Impact factor: 4.379