A methyl-deficient diet fed to rats during the pre- and peri-conception periods of development modifies the hepatic prot
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RESEARCH PAPER
A methyl-deficient diet fed to rats during the pre- and periconception periods of development modifies the hepatic proteome in the adult offspring Christopher A. Maloney • Susan M. Hay • Martin D. Reid • Gary Duncan • Fergus Nicol Kevin D. Sinclair • William D. Rees
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Received: 6 October 2011 / Accepted: 2 August 2012 Ó Springer-Verlag 2012
Abstract A methyl-deficient diet (MD) lacking folic acid and the associated methyl donors choline and methionine, fed to the laboratory rat during the periods of oocyte and embryo development, has been shown to programme glucose metabolism in the offspring. The hepatic proteome of the male offspring of female rats fed MD diets for 3 weeks prior to mating and for the first 5 days of gestation has been examined by 2-dimensional gel electrophoresis. Three groups of differentially abundant proteins associated with energy metabolism, amino acid metabolism and antioxidant defence were identified in the soluble proteins extracted from the liver from the MD offspring at both 6 and 12 months of age. Altered mitochondrial activity in other programming models leads to a similar pattern of differential protein abundance. Two of the differentially abundant proteins were identified as GAPDH and PGK-1 by mass spectrometry. Western blotting showed that there
Present Address: C. A. Maloney School of Medical Sciences, Faculty of Medicine, The University of New South Wales, Sydney, NSW 2052, Australia
were multiple isoforms of both proteins with similar molecular weights but different isoelectric points. The differentially abundant spots reduced in the MD offspring corresponded to minor isoforms of GAPDH and PGK-1. The levels of PPAR-alpha, SREBP and glucocorticoid receptor mRNAs associated with other models of prenatal programming were unchanged in the MD offspring. The data suggest that a diet deficient in folic acid and associated methyl donors fed during the peri-conception and early preimplantation periods of mammalian development affects mitochondrial function in the offspring and that the posttranslational modification of proteins may be important. Keywords Foetal programming Methylation PEPCK Mitochondria Abbreviations ACC-1 HOMA L-CPT-1 GAPDH MD PEPCK
S. M. Hay M. D. Reid G. Duncan F. Nicol W. D. Rees (&) The Rowett Institute of Nutrition and Health, The University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, Scotland, UK e-mail: [email protected]
PGC-1a PGK1 PPAR-a and PPAR-c
K. D. Sinclair School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicestershire LE12 5RD, UK
Udpgdh GccR oGTT
SREBP-1c
Acetyl-CoA carboxylase Homoeostasis model Carnitine palmitoyl transferase Glyceraldehyde-3-phosphate dehydrogenase Methyl deficient Phosphoenolpyruvate carboxykinase PPAR-c co-activator-1a Phosphoglycerate kinase Peroxisome proliferator-activated receptors alpha and gamma Sterol response element binding protein UDP-glucose dehydrogenase Glucocorticoid receptor Oral glucose tolerance test
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Genes Nutr
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