Exploration of glycogen deposition disorders in low-body-weight fetuses in a pig model

<p>Glucose is a vital energy source for the fetus, storing any surplus as glycogen. Neonates experiencing intrauterine growth restriction exhibit decreased hepatic glycogen levels. Consequently, the regulation of glycogen deposition may hold immense significance in fetal development, yet the intricacies of glycogen deposition homeostasis remain poorly understood. Here, we aimed to explore the differences in fetal glycogen deposition and its potential mechanisms using fetal pigs with the lowest (L) and medium (M) body weights on gestation days 60 (GD 60) and 90 (GD 90). We observed higher hepatic glycogen concentrations in the L group on GD 60, which correlated with higher hepatic glucose levels and glycogen synthase activity. In addition, our investigation using RNA-seq and immortalized fetal pig liver cells revealed that the cAMP signaling pathway ranked prominently in the KEGG enrichment analysis of differentially expressed genes. Notably, this pathway was relatively suppressed in the livers of L group pigs on GD 60, compared to the M group. The cAMP signaling pathway suppression resulted in glycogen concentration upregulation in our <i>in vitro</i> model. Overall, our findings suggest that glucose needed for fetal development deposited abnormally in the liver may hinder the growth of low-body-weight fetuses at mid-gestation. Furthermore, we have identified the cAMP signaling pathway as a pivotal regulator of hepatic glycogen deposition homeostasis in fetuses at mid-gestation, offering a novel perspective on the factors contributing to delayed fetal growth.</p>