Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 24, Issue 2, Pages 484-495Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2012.01.011
Keywords
Protein restriction; Protein excess; Maternal diet; Foetal programming; Pig; Intrauterine growth restriction
Funding
- German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung, BMBF, Germany)
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Maternal nutrition during gestation has important effects on offspring gene expression mediated by DNA methylation. In order to evaluate the effect of restricted and excess protein intake during gestation, hepatic gene expression and DNA methylation of key metabolic genes NR3C1, PPAR alpha, HMGCR, PGC1 alpha, INSR and CYP2C34 were investigated. Liver samples of German Landrace offspring were collected at Gestational Day 95, at birth, at weaning and from finisher pigs. Gene expression in foetal liver revealed significant differences between the control group (LP) and the low-protein group (LP) in HMGCR (P<.0001), INSR (P=.0003), NR3C1 (P=.020) and PGC1 alpha (P=.003). At birth INSR (P=.032), PPAR alpha (P=.0006) and CYP2C34 (P<.0001) showed significant differences between LP and CO. CYP2C34 was significantly increased in the high-protein group (HP) compared to CO (P=.001). At weaning, INSR was significantly higher expressed in LP than in CO (P=.018). HMGCR showed a significant decrease of transcript amount in HP compared to CO (P=.0006). Furthermore, we studied the question whether gene expression differences between distinct diet groups are a result of differential DNA methylation status. CpG sites in the 5'-flanking region of CYP2C34 showed a significant positive correlation with transcript amount in LP (nt -137: R=0.67, P<.0001; nt -112: R=0.54, P=.003). In NR3C1 methylation, differences in the CpG island were negatively correlated with gene expression data in LP (R=-0.34, P=.032). The mean of methylation of PPAR alpha over CpG sites from nt -220 to -11 was significantly increased in the LP group compared with CO (P=.043). These data suggest an influence of DNA methylation in nutrient-dependent transcriptional regulation of NR3C1, PPAR alpha and CYP2C34. (c) 2013 Elsevier Inc. All rights reserved.
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