Decreased UCP-1 expression in beige adipocytes from adipose-derived stem cells of type 2 diabetes patients associates with mitochondrial ROS accumulation during obesity

Abstract Objective Adipose derived stem cells (ADSC) are defective in metabolic disorders in various functionalities and properties including differentiation, multipotent state, metabolism and immunomodulation. However, the role of ADSC beiging potential in promoting of type 2 diabetes mellitus (T2DM) development remains unclear. Here we uncover association between potential of subcutaneous ADSC to beige differentiation and T2DM in patients with obesity. Methods ADSC were isolated from subcutaneous adipose tissue of patients with long morbid obesity (BMI > 35 kg/m2) and normal glucose tolerance (NGT) or T2DM. ADSC were differentiated into white or beige adipocytes and levels of thermogenic markers, lipid metabolism and electron transport chain (ETC) genes was analyzed by Western blotting and RT-PCR. ROS production was estimated by fluorescent microscopy. Results We have shown decreased UCP-1 expression in beige adipocytes from T2DM patients. Nevertheless, signal and expression activities of lipolysis were equal in NGT and T2DM beige adipocytes. Expression analysis of ETC genes also has not shown any statistically significant differences. Interestingly, we revealed increased mitochondrial ROS production in T2DM beige adipocytes during beige differentiation. Conclusions In summary, compromised UCP1 expression in beige adipocytes of T2DM patients may cause increase of mitochondrial ROS. Elevated oxidative level is liable to act as damaging mechanism leading to insulin resistance or, alternatively, serve as compensatory mechanism for thermogenesis activation.