Maternal Protein Restriction and Post-Weaning High-Fat Feeding Alter Plasma Amino Acid Profiles and Hepatic Gene Expression in Mice Offspring.

Maternal undernutrition during pregnancy is closely associated with epigenetic changes in the child, and it affects the development of obesity throughout the child's life. Here, we investigate the effect of fetal low protein exposure and post-weaning high-fat consumption on plasma amino acid profiles and hepatic gene expression. Mother C57BL/6J mice were fed a 20% (CN) or 9% (LP) casein diet during pregnancy. After birth, the male offspring of both these groups were fed a high-fat diet (HF) from 6 to 32 weeks. At 32 weeks, the final body weight between the two groups remained unchanged, but the LP-HF group showed markedly higher white fat weight and plasma leptin levels. The LP-HF group exhibited a significant increase in the concentrations of isoleucine, leucine, histidine, phenylalanine, serine, and tyrosine. However, no differences were observed in the lipid content in the liver. According to the hepatic gene expression analysis, the LP-HF group significantly upregulated genes involved in the chromatin modification/organization pathways. Thus, maternal low protein and a post-weaning high-fat environment contributed to severe obesity states and changes in gene expression related to hepatic chromatin modification in offspring. These findings provide novel insights for the prevention of lifestyle-related diseases at the early life stage.