Preadipocytes of type 2 diabetes subjects display an intrinsic gene expression profile of decreased differentiation capacity

Objective: Insulin resistance and type 2 diabetes mellitus (T2DM) are associated with increased adipocyte size, altered secretory pattern and decreased differentiation of preadipocytes. In this study, we identified the underlying molecular processes in preadipocytes of T2DM patients, a characteristic for the development of T2DM. Design and Participants: Preadipocyte cell cultures were prepared from subcutaneous fat biopsies of seven T2DM patients (age 53+/-12 years; body mass index (BMI) 34+/-5 kg m-2) and nine control subjects (age 51+/-12 years; BMI 30+/-3 kg m-2). Microarray analysis was used to identify altered processes between the T2DM and control preadipocytes. Results: Gene expression profiling showed changed expression of transcription regulators involved in adipogenesis and in extracellular matrix remodeling, actin cytoskeleton and integrin signaling genes, which indicated decreased capacity to differentiate. Additionally, genes involved in insulin signaling and lipid metabolism were downregulated, and inflammation/apoptosis was upregulated in T2DM preadipocytes. Conclusion: Decreased expression of genes involved in differentiation can provide a molecular basis for the reduced adipogenesis of preadipocytes of T2DM subjects, leading to reduced formation of adipocytes in subcutaneous fat depots, and ultimately leading to ectopic fat storage.