Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/62858
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dc.contributor.authorNg, S.-
dc.contributor.authorLin, R.-
dc.contributor.authorLaybutt, D.-
dc.contributor.authorBarres, R.-
dc.contributor.authorOwens, J.-
dc.contributor.authorMorris, M.-
dc.date.issued2010-
dc.identifier.citationNature, 2010; 467(7318):963-U103-
dc.identifier.issn0028-0836-
dc.identifier.issn1476-4687-
dc.identifier.urihttp://hdl.handle.net/2440/62858-
dc.description.abstractThe global prevalence of obesity is increasing across most ages in both sexes. This is contributing to the early emergence of type 2 diabetes and its related epidemic. Having either parent obese is an independent risk factor for childhood obesity. Although the detrimental impacts of diet-induced maternal obesity on adiposity and metabolism in offspring are well established, the extent of any contribution of obese fathers is unclear, particularly the role of non-genetic factors in the causal pathway. Here we show that paternal high-fat-diet (HFD) exposure programs β-cell 'dysfunction' in rat F(1) female offspring. Chronic HFD consumption in Sprague-Dawley fathers induced increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had an early onset of impaired insulin secretion and glucose tolerance that worsened with time, and normal adiposity. Paternal HFD altered the expression of 642 pancreatic islet genes in adult female offspring (P < 0.01); genes belonged to 13 functional clusters, including cation and ATP binding, cytoskeleton and intracellular transport. Broader pathway analysis of 2,492 genes differentially expressed (P < 0.05) demonstrated involvement of calcium-, MAPK- and Wnt-signalling pathways, apoptosis and the cell cycle. Hypomethylation of the Il13ra2 gene, which showed the highest fold difference in expression (1.76-fold increase), was demonstrated. This is the first report in mammals of non-genetic, intergenerational transmission of metabolic sequelae of a HFD from father to offspring.-
dc.description.statementofresponsibilitySheau-Fang Ng, Ruby C. Y. Lin, D. Ross Laybutt, Romain Barres, Julie A. Owens & Margaret J. Morris-
dc.language.isoen-
dc.publisherNature Publishing Group-
dc.rights©2010 Macmillan Publishers Limited. All rights reserved.-
dc.subjectCytoskeleton-
dc.subjectAnimals-
dc.subjectRats-
dc.subjectRats, Sprague-Dawley-
dc.subjectDiabetes Mellitus, Type 2-
dc.subjectGlucose Intolerance-
dc.subjectObesity-
dc.subjectBody Weight-
dc.subjectCations-
dc.subjectInsulin-
dc.subjectGlucose-
dc.subjectDietary Fats-
dc.subjectAdenosine Triphosphate-
dc.subjectGlucose Tolerance Test-
dc.subjectDiet-
dc.subjectGene Expression Profiling-
dc.subjectFathers-
dc.subjectPaternal Exposure-
dc.subjectSignal Transduction-
dc.subjectCell Cycle-
dc.subjectApoptosis-
dc.subjectDNA Methylation-
dc.subjectGene Expression Regulation-
dc.subjectEpigenesis, Genetic-
dc.subjectAging-
dc.subjectHomeostasis-
dc.subjectLitter Size-
dc.subjectFemale-
dc.subjectMale-
dc.subjectAdiposity-
dc.subjectInsulin-Secreting Cells-
dc.subjectInsulin Secretion-
dc.titleChronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring-
dc.title.alternativeChronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring-
dc.typeJournal article-
dc.identifier.doi10.1038/nature09491-
dc.relation.grantNHMRC-
pubs.publication-statusPublished-
dc.identifier.orcidOwens, J. [0000-0002-7498-1353]-
Appears in Collections:Aurora harvest 5
Obstetrics and Gynaecology publications

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