The influence of living alone on epigenomic and transcriptomic changes of pancreatic islets derived from an inbred strain of mice with spontaneous diabetes and moderate obesity

Social relationships are related to disease and mortality risk, although the exact mechanisms remain unknown. KK mouse is a model of type 2 diabetes associated with moderate obesity. In light of the evidence that living alone is a risk factor for type 2 diabetes in humans, it has also been reported that single-housing of male KK mice exhibit accelerated weight gain and onset of diabetes. Here, we report the application of next-generation sequencing technology for high-throughput profiling of H3K27ac and transcriptome analysis in pancreatic islets derived from KK mice housed under different stocking densities. We find genomic regions showing various changes in acetylation of histone H3K27 in response to 2 weeks of single-housing compared to group-housed controls, which is significantly associated with differential gene expression. Among different types of differential H3K27ac regions, those showing decrease are particularly intriguing because of the association with pancreatic beta cell function, binding motifs of critical transcription factors responsible for human diabetes (type 2 diabetes and MODY), and GWAS susceptibility loci for type 2 diabetes and related diseases. These findings provide insights into epigenetic mechanisms by which living alone influences on increased risk of type 2 diabetes.