title: High fructose consumption induces DNA methylation at PPARα and CPT1A promoter regions in the rat liver.
abstract: DNA methylation status is affected by environmental factors, including nutrition. Fructose consumption is considered a risk factor for the conditions that make up metabolic syndrome such as dyslipidemia. However, the pathogenetic mechanism by which fructose consumption leads to metabolic syndrome is unclear. Based on observations that epigenetic modifications are closely related to induction of metabolic syndrome, we hypothesized that fructose-induced metabolic syndrome is caused by epigenetic alterations. Male SD rats were designated to receive water or 20% fructose solution for 14 weeks. mRNA levels for peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1A (CPT1A) was analyzed using Real-time PCR. Restriction digestion and real-time PCR (qAMP) was used for the analysis of DNA methylation status. Hepatic lipid accumulation was also observed by fructose intake. Fructose feeding also significantly decreased mRNA levels for PPARα and CPT1A. qAMP analysis demonstrated the hypermethylation of promoter regions of PPARα and CTP1A genes. Fructose-mediated attenuated gene expression may be mediated by alterations of DNA methylation status, and pathogenesis of metabolic syndrome induced by fructose relates to DNA methylation status.
authors.affiliation: Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Biochemistry, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Munetsuna
authors.affiliation: Department of Hygiene, Fujita Health University School of Medicine, Toyoake, Japan. Electronic address: hyamada@fujita-hu.ac.jp.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University Hospital, Toyoake, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ando
authors.affiliation: Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors.forename: Mirai
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Taromaru
authors.affiliation: Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors.forename: Ayuri
authors.initials: A
authors.lastname: Nagura
authors.affiliation: Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Department of Public Health, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Teradaira
authors.affiliation: Department of Hygiene, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics*; D019175:DNA Methylation; D005632:Fructose / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D047493:PPAR alpha / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D047493:PPAR alpha; D012333:RNA, Messenger; D005632:Fructose; D002334:Carnitine O-Palmitoyltransferase; C583748:carnitine palmitoyltransferase-1a, rat
keywords: Corn syrup; Dyslipidemia; Epigenetics; Gene expression; Metabolic syndrome; Nutrition