Figure 3. Metabolic Phenotype of Prenatally Undernourished Rats and Changes in Promoter Methylation and Gene Expression.

The offspring of rats fed a protein-restricted diet (PR) show reduced promoter methylation and increased messenger RNA (mRNA) expression of the transcription factor peroxisome proliferator-activated receptor α (PPAR-α) in the liver, as compared with control rats fed a normal diet (Panel A). Increased PPAR-α expression is associated with increased expression of the downstream enzyme acyl-CoA oxidase (AOX), a key enzyme in fatty acid β oxidation, and increased circulating concentrations of the ketone β-hydroxybutyrate. These effects were prevented by supplementation of the maternal diet with folate (PR+F). The offspring of rats in the PR group show reduced promoter methylation and increased mRNA expression of the glucocorticoid receptor (GR) in the liver, associated with increased expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and increased blood glucose levels (Panel B). Again, the effects are not seen in offspring of rats in the PR+F group. P values are shown for the comparison of the PR group with the control group; the P values for the comparison of the PR+F group with the control group indicated no significant difference. Data are means; T bars indicate SEs. Adapted from Lillycrop et al.^49,70 and Burdge et al.⁷¹