A transcriptomic analysis of primary mature adipocytes from lean, obese, and type 2 diabetic subjects: role of the extracellular matrix. A transcriptomic analysis of primary mature adipocytes from lean, obese, and type 2 diabetic subjects: role of the extracellular matrix

Type 2 diabetes is associated with obesity, and is characterized by insulin resistance in target tissues of the hormone combined with insufficient systemic insulin. Insulin resistance apparently begins in subcutaneous adipocytes that fail to further accumulate triacylglycerol. To understand the pathogenesis of transition from lean to obesity and to diabetes, we performed transcriptome profiling by RNA-sequencing of isolated primary human adipocytes. Half of identified transcripts were protein-coding and shared between individuals, while non-protein-coding transcripts were subject specific. Differential gene expression between lean and diabetes reflected corresponding changes in 7 of 12 characterized insulin-signaling proteins. In the tissue, adipocytes are surrounded by extracellular matrix (ECM) providing a dynamic scaffold. However, excess ECM is implicated in obesity and diabetes. Bioinformatic analyses of transcriptomes revealed major upregulation of genes related to ECM in obese compared with lean, which was reversed in diabetes. However, biochemical analysis of adipose tissue demonstrated reduced ECM in obesity or diabetes compared with lean. We conclude that marked changes in the adipocyte transcriptome related to ECM do not reflect global adipose tissue fibrosis, but likely control the pericellular milieu surrounding the adipocyte; and excess ECM is not a feature of subcutaneous adipose tissue in obesity or diabetes. Overall design: Adipocyte mRNA profiles from lean, obese and type 2 diabetic subjects, 6 samples each >>>Submitter states that the raw data cannot be made available due to patient privacy concerns<<<