Maternal low-protein diet alters hepatic lipid accumulation and gene expression related to glucose metabolism in young adult mouse offspring fed a postweaning high-fat diet

Abstract

Maternal consumption of low-protein (LP) diet during pregnancy has been demonstrated to increase the chances of adult offspring developing metabolic syndrome, and this risk can be exacerbated when the postnatal diets do not align with the prenatal conditions. However, in our previous study, focusing on serum parameters and gene expression patterns within adipose tissue, we discovered the presence of "healthy obesity" in young adult offspring from dams that were fed an LP, as a response to a postweaning high-fat (HF) diet. Here, we subsequently investigated the role played by the liver and skeletal muscle in alleviation of insulin resistance in male offspring that were fed either control (C/C group) or HF diet (C/HF and LP/HF groups) for 22 weeks. While a postweaning HF diet increased liver weight and hepatic triglyceride (TG) and cholesterol levels in offspring of control dams, these levels were lower in the LP/HF group compared to the C/HF group. Analysis of the liver transcriptome identified 430 differentially expressed genes (DEGs) in the LP/HF and C/HF comparison. Especially, downregulated DEGs were enriched in carbohydrate metabolism and the levels of DEGs were significantly correlated with the levels of markers for serum glucose homeostasis and hepatic lipid accumulation. In the LP/HF group compared to the C/HF group, there was a decrease in the gastrocnemius muscle weight, while no differences were observed in gene expression levels associated with muscle fiber phenotype, mitochondrial function, and inflammation. In conclusion, maternal LP diet induced changes in lipid and glucose metabolism within the liver, similar to what was observed in adipose tissue, while there were no alterations in metabolic functions in the skeletal muscle in young offspring mice fed an HF diet. Further research that investigating the enduring impact of nutritional transition on offspring is essential to gain a comprehensive grasp of developmental programming throughout their entire lifespan.

Keywords: Glucose metabolism; Liver; Mouse offspring; Muscle; Nutritional transition; Transcriptome.