Feeding a protein-restricted diet during pregnancy induces altered epigenetic regulation of peroxisomal proliferator-activated receptor-α in the heart of the offspring

Abstract

Impaired flexibility in the use of substrates for energy production in the heart is implicated in cardiomyopathy. We investigated the effect of maternal protein restriction during pregnancy in rats on the transcription of key genes in cardiac lipid and carbohydrate metabolism in the offspring. Rats were fed protein-sufficient or protein-restricted (PR) diets during pregnancy. Triacylglycerol concentration in adult (day 105) heart was altered by maternal protein intake contingent on post-weaning fat intake and sex. mRNA expression of peroxisomal proliferator-activated receptor (PPAR)-α and carnitine palmitoyltransferase-1 was increased by the maternal PR diet in adult, but not neonatal, offspring. PPARα promoter methylation was lower in adult and neonatal heart from PR offspring. These findings suggest that prenatal nutrition alters the future transcriptional regulation of cardiac energy metabolism in the offspring through changes in epigenetic regulation of specific genes. However, changes in gene functional changes may not be apparent in early life.

Fig. 1

PPARα mRNA expression (open bars) and promoter methylation (solid bars) in (a) male and (b) female adult and neonatal heart. Values are mean ± 1SD, n = 7 – 15 samples per group. LF, low fat post-weaning diet; HF; PS, maternal protein-sufficient diet; PR, maternal protein-restricted diet. Values which are significantly different (P < 0.05) within an age group for each outcome are indicated by different letters. *Indicates statistically significant differences (P < 0.001) by Student’s unpaired t-test between hearts from adults fed the LF diet after weaning and neonatal heart within the same maternal dietary group.