Adipose tissue plays an important role in metabolism and homoeostasis. Perturbations in the nature and amount of adipose tissue have serious health consequences for individuals and society. An increase in visceral adipose tissue (VAT) is associated with diseases ranging from Type 2 Diabetes Mellitus to cancer, while subcutaneous adipose tissue (SAT) may have a protective effect. A number of genes have been identified to be differentially expressed between these two adipose depots, however mechanisms controlling this differential expression is poorly understood. To characterize potential developmental differences in adipocytes from different depots we analysed both the transcriptomes and methylomes of adipocyte cells purified from SAT and VAT of three lean females. Comparisons were also made between whole visceral adipose tissue and leukocytes from the same individuals as a reference. Methylomes were mapped using both whole genome bisulphite sequencing and Illumina 450K arrays and gene expression characterized using Affymetrix Exon2.0 arrays and strand-specific RNA-Seq.
We found that methylation profiles of each sample type were highly consistent between patients and clearly segregated cell types. While distinct DNA methylation differences were found between purified visceral adipocytes and whole visceral adipose tissues, they clustered closely and separated clearly from subcutaneous adipocytes. Anenrichment of promoter differential methylation compared to other genic regions also occurred between visceral and subcutaneous adipocytes. Analysis of both differential methylation and differential gene expression between adipocytes identified development, lipid metabolism, inflammatory response, neurological system processes and proliferation as pathway categories. The observed methylation differences indicate the separate developmental origins of subcutaneous and visceral adipose cells, while differences in expression of lipid metabolism and inflammatory response genes may reflect functional and environmental differences respectively between the two tissues. The primary epigenomic profiles of purified normal adipocytes form the basis for understanding the functional role of different fat depots in metabolic disease.