A methyl-deficient diet fed to rats during the pre- and peri-conception 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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)181-190
Number of pages10
JournalGenes & Nutrition
Volume8
Issue number2
Early online date21 Aug 2012
DOIs
Publication statusPublished - Mar 2013

Fingerprint

Proteome
Diet
Liver
Proteins
Folic Acid
Protein Isoforms
Embryonic and Fetal Development
PPAR alpha
Glucocorticoid Receptors
Isoelectric Point
Post Translational Protein Processing
Choline
Methionine
Energy Metabolism
Oocytes
Embryonic Development
Electrophoresis
Mass Spectrometry
Antioxidants
Molecular Weight

Keywords

  • foetal programming
  • methylation
  • PEPCK
  • mitochondria

Cite this

A methyl-deficient diet fed to rats during the pre- and peri-conception periods of development modifies the hepatic proteome in the adult offspring. / Maloney, Christopher A; Hay, Susan M; Reid, Martin D; Duncan, Gary; Nicol, Fergus; Sinclair, Kevin D; Rees, William D.

In: Genes & Nutrition, Vol. 8, No. 2, 03.2013, p. 181-190.

Research output: Contribution to journalArticle

Maloney, Christopher A ; Hay, Susan M ; Reid, Martin D ; Duncan, Gary ; Nicol, Fergus ; Sinclair, Kevin D ; Rees, William D. / A methyl-deficient diet fed to rats during the pre- and peri-conception periods of development modifies the hepatic proteome in the adult offspring. In: Genes & Nutrition. 2013 ; Vol. 8, No. 2. pp. 181-190.
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