Supplementation of a maternal low-protein diet in rat pregnancy with folic acid ameliorates programming effects upon feeding behaviour in the absence of disturbances to the methionine-homocysteine cycle.

Maternal protein restriction in rat pregnancy is associated with altered feeding behaviour in later life. When allowed to self-select their diet, rats subject to prenatal undernutrition show an increased preference for fatty foods. The main aim of the present study was to evaluate the contribution of folic acid in the maternal diet to programming of appetite, since disturbances of the folate and methionine-homocysteine cycles have been suggested to impact upon epigenetic regulation of gene expression and hence programme long-term physiology and metabolism. Pregnant rats were fed diets containing either 9 or 18 % casein by weight, with folate provided at either 1 or 5 mg/kg diet. Adult male animals exposed to low protein (LP) in fetal life exhibited increased preference for high-fat food. Providing the higher level of folate in the maternal diet prevented this effect of LP, but offspring of rats fed 18 % casein diet with additional folate behaved in a similar manner to LP-exposed animals. Among day 20 gestation fetuses, it was apparent that both protein restriction and maternal folate supplementation could have adverse effects upon placental growth. Examination of methionine-homocysteine and folate cycle intermediates, tissue glutathione concentrations and expression of mRNA for methionine synthase, DNA methyltransferase 1 and methyltetrahydrofolate reductase revealed no gross disturbances of folate and one-carbon metabolism in either maternal or fetal tissue. The present findings indicated that any role for DNA methylation in programming of physiology is not related to major perturbations of folate metabolism, and is likely to be gene-specific rather than genome-wide.