Epigenetic and transcriptomic characterization of pure adipocyte fractions from obese pigs identifies candidate pathways controlling metabolism

Reprogramming of adipocyte function in obesity is implicated in metabolic disorders like type 2 diabetes. Here, we used the pig, an animal model sharing many physiological and pathophysiological similarities with humans, to perform in depth epigenomic and transcriptomic characterization of pure adipocyte fractions. Using a combined DNA methylation capture sequencing and Reduced Representation bisulfite sequencing (RRBS) strategy, we identified 2479 differentially methylated regions (DMRs) located at close proximity to-, or within genes. By sequencing of the transcriptome from the same adipocyte cells, we identified 276 differentially expressed transcripts with at least one or more DMRs. These transcripts were over-represented in gene pathways related to MAPK, insulin and adipocytokine signaling. Using a candidate gene approach, we further characterized 13 genes potentially regulated by DNA methylation and identified putative transcription factor binding sites that could be affected by the differential methylation in obesity. Our data constitute a valuable resource for further investigations aiming to delineate the epigenetic etiology of metabolic disorders. MeDip-seq, RRBS-seq and RNA-seq of adipocytes from lean and obese pigs.