title: High-fat diet disrupts metabolism in two generations of rats in a parent-of-origin specific manner.
abstract: Experimental and epidemiological evidence demonstrate that ancestral diet might contribute towards offspring health. This suggests that nutrition may be able to modify genetic or epigenetic information carried by germ cells (GCs). To examine if a parental high fat diet (HFD) influences metabolic health in two generations of offspring, GC-eGFP Sprague Dawley rats were weaned onto HFD (45% fat) or Control Diet (CD; 10% fat). At 19 weeks, founders (F0) were bred with controls, establishing the F1 generation. HFD resulted in 9.7% and 14.7% increased weight gain in male and female F0 respectively. F1 offspring of HFD mothers and F1 daughters of HFD-fed fathers had increased weight gain compared to controls. F1 rats were bred with controls at 19 weeks to generate F2 offspring. F2 male offspring derived from HFD-fed maternal grandfathers exhibited increased adiposity, plasma leptin and luteinising hormone to testosterone ratio. Despite transmission via the founding male germline, we did not find significant changes in the F0 intra-testicular GC transcriptome. Thus, HFD consumption by maternal grandfathers results in a disrupted metabolic and reproductive hormone phenotype in grandsons in the absence of detectable changes in the intra-testicular GC transcriptome.
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, EH16 4TJ, UK.
authors.forename: T J G
authors.initials: TJG
authors.lastname: Chambers
authors.affiliation: MRC Computational Genomics Analysis and Training, Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK.
authors.forename: M D
authors.initials: MD
authors.lastname: Morgan
authors.affiliation: MRC Computational Genomics Analysis and Training, Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK.
authors.forename: A H
authors.initials: AH
authors.lastname: Heger
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, EH16 4TJ, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Sharpe
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, QMRI, 47 Little France Crescent, EH16 4TJ, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Drake
mesh_terms: D050154:Adiposity / Q000235:genetics; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D020869:Gene Expression Profiling; D020738:Leptin / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013737:Testis / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D014886:Weaning; D015430:Weight Gain
chemical_list: D020738:Leptin; D013739:Testosterone; D007986:Luteinizing Hormone