Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations

Epidemiological studies and experimental models show that maternal nutritional constraint during pregnancy alters the metabolic phenotype of the offspring and that this can be passed to subsequent generations. In the rat, induction of an altered metabolic phenotype in the liver of the F1 generation by feeding a protein-restricted diet (PRD) during pregnancy involves the altered methylation of specific gene promoters. We therefore investigated whether the altered methylation of PPARα and glucocorticoid receptor (GR) promoters was passed to the F2 generation. Females rats (F0) were fed a reference diet (180 g/kg protein) or PRD (90 g/kg protein) throughout gestation, and AIN-76A during lactation. The F1 offspring were weaned onto AIN-76A. F1 females were mated and fed AIN-76A throughout pregnancy and lactation. F1 and F2 males were killed on postnatal day 80. Hepatic PPARα and GR promoter methylation was significantly (P