Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia. The prevalence of type 2 diabetes mellitus (T2DM) has increased worldwide. In the last few decades, with the rise of genome-wide association studies, accumulating studies have demonstrated that genetic factors contribute to the pathogenesis of T2DM. However, genetic loci can account for only 15% of T2DM cases [1]. Therefore, environmental factors are reported to play very important roles in the development of T2DM. However, the food environment is one of the most important challenges for T2DM [2]. Accumulating studies have demonstrated that a maternal low-protein diet during pregnancy and/or lactation may strongly increase the risk of T2DM in offspring [3,4]. The maternal low-protein diet (5%–10% protein) model has been one of the most extensively used models of maternal under-nutrition [5,6]. By using this model, emerging evidence has shown that epigenetic modifications may be one of the underlying mechanisms explaining the association between maternal protein restriction and T2DM in adult offspring. Epigenetic modifications include noncoding RNA, DNA methylation and histone modifications. DNA methylation has been implicated in the development of diabetes in the offspring of mothers with under-nutrition during pregnancy [7,8]. Our previous study demonstrated that a maternal low-protein diet combined with postweaning high-fat feeding predisposes male offspring to impaired glucose metabolism and hypothalamic POMC hypomethylation [7]. In addition to DNA methylation, noncoding RNAs (ncRNAs), as one type of epigenetic modification, have also attracted significant interest because they contribute to the development of T2DM [9,10]. The types of functional ncRNAs include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). lncRNAs, a class of RNA transcripts longer than 200 nucleotides, can regulate the expression of protein-coding genes at the transcriptional and translational levels [11]. Studies have demonstrated that lncRNAs may regulate pancreatic β-cell morphology and insulin secretion during the development of diabetes mellitus [12,13]. However, studies exploring whether a maternal low-protein diet could regulate lncRNAs in islets in adult offspring are limited.

In our current study, we explored a trans-generational mouse model of maternal low-protein diet and performed a high-throughput microarray of lncRNAs in islets from adult offspring exposed to a maternal low-protein diet. We revealed the altered expression of key lncRNAs in islets and impaired glucose metabolism in adult offspring that were exposed to a maternal low-protein diet during pregnancy and lactation.