A maternal low-protein diet impaired glucose metabolism and altered the lncRNA profiles of islets in adult offspring

Abstract

A maternal low-protein diet during pregnancy can increase children's susceptibility to diabetes mellitus in adulthood. However, whether long noncoding RNAs (lncRNAs) in islets participate in the development of diabetes in adult offspring following maternal protein restriction is not fully understood. Female mice were fed a low-protein (LP) diet or control diet throughout gestation and lactation. The male offspring were then randomly divided into two groups according to maternal diet: offspring from control diet group dams (Ctrl group) and offspring from LP group dams (LP group). We observed the glucose metabolism of adult offspring. A lncRNA microarray was constructed for the islets from the LP group and Ctrl group to explore the differently expressed lncRNAs. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analyses were subsequently used to predict the functions of the differently expressed lncRNAs. The body weight from birth to 12 weeks of age was significantly lower in the LP offspring. Adult LP offspring exhibited impaired glucose tolerance and decreased insulin secretion, consistent with the reduction in β-cell proliferation. According to the lncRNA microarray, four lncRNAs, three upregulated lncRNAs, and one downregulated lncRNA were differently expressed in LP offspring islets compared with Ctrl offspring. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these differentially expressed lncRNAs were mostly associated with the hypoxia-inducible factor-1α signaling pathway. Additionally, we validated the expression of these four differentially expressed lncRNAs via quantitative real-time polymerase chain reaction. Our findings demonstrated the expression patterns of lncRNAs in islets from adult offspring of mothers who consumed a maternal low-protein diet.