Abstract
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.
Highlights
Obesity is a major risk factor for many chronic diseases
There were no significant differences in body weight changes and food intake between the two groups (Figure 1a,b)
The weights of mesenteric fat and epididymal fat tended to be higher in the LP-high-fat diet (HF) group (Figure 1d,e); the retroperitoneal fat weight did not differ between the two groups (Figure 1f)
Summary
Obesity is a major risk factor for many chronic diseases. Maternal undernutrition during pregnancy and lactation changes the child’s epigenetic state; it is one of the long-term risk factors for children’s obesity [1,2]. Several animal experiments have indicated that maternal undernutrition during pregnancy and high-fat feeding during post-weaning results in serious obesity when the offspring grow to become adults [4–6]. These studies investigated the effects of the interscapular brown adipose tissue [5], white adipose tissue [6], and the hypothalamus [4]. It is important to clarify the mechanism by which maternal low-protein and offspring high-fat consumption increase the risk of obesity
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