title: The effects of paternal high-fat diet exposure on offspring metabolism with epigenetic changes in the mouse adiponectin and leptin gene promoters.
abstract: Recent studies have demonstrated that epigenetic changes resulting from malnutrition might play important roles in transgenerational links with metabolic diseases. Previously, we observed that exposure to a high-fat diet (HFD) in utero caused a metabolic syndrome-like phenomenon through epigenetic modifications of the adiponectin and leptin genes that persisted for multiple generations. Recent etiological studies indicated that paternal BMI had effects on offspring BMI that were independent of but additive to maternal BMI effects. Thus, we examined whether paternal HFD-induced obesity affected the metabolic status of offspring through epigenetic changes in the adiponectin and leptin genes. Additionally, we investigated whether a normal diet during subsequent generations abolished the epigenetic changes associated with paternal HFD exposure before conception. We observed the effects of paternal HFD exposure before conception over multiple generations on offspring metabolic traits, including weight and fat gain, glucose intolerance, hypertriglyceridemia, abnormal adipocytokine levels, hypertension, and adiponectin and leptin gene expression and epigenetic changes. Normal diet consumption by male offspring during the subsequent generation following paternal HFD exposure diminished whereas consumption for two generations completely abolished the effect of paternal HFD exposure on metabolic traits and adipocytokine promoter epigenetic changes in the offspring. The effects of paternal HFD exposure on offspring were relatively weaker than those following HFD exposure in utero. However, paternal HFD exposure had an additive metabolic effect for two generations, suggesting that both paternal and maternal nutrition might affect offspring metabolism through epigenetic modifications of adipocytokine genes for multiple generations.
authors.affiliation: Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Masuyama
authors.affiliation: Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mitsui
authors.affiliation: Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Eguchi
authors.affiliation: Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Tamada
authors.affiliation: Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hiramatsu
mesh_terms: D054392:Adipokines / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics*; D000818:Animals; D047369:Chromatin Immunoprecipitation; D059305:Diet, High-Fat; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D018149:Glucose Intolerance / Q000235:genetics*; D006973:Hypertension / Q000235:genetics; D015228:Hypertriglyceridemia / Q000235:genetics*; D020738:Leptin / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D051379:Mice; D009765:Obesity / Q000235:genetics; D018812:Paternal Exposure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015430:Weight Gain / Q000235:genetics
chemical_list: D054392:Adipokines; D052242:Adiponectin; C499919:Adipoq protein, mouse; D020738:Leptin; D012333:RNA, Messenger
keywords: adiponectin; epigenetics; high-fat diet; leptin; metabolic syndrome