Svetlana Michurina1, Iurii Stafeev2, Nikita Podkuychenko3, Igor Sklyanik4, Ekaterina Shestakova4, Kamil Yah'yaev5, Anatoliy Yurasov5, Elizaveta Ratner6, Mikhail Menshikov7, Yelena Parfyonova8, Marina Shestakova4. 1. National Medical Research Center for Cardiology, Moscow, Russia; M.V.Lomonosov Moscow State University, Moscow, Russia. Electronic address: michurina192@gmail.com. 2. National Medical Research Center for Cardiology, Moscow, Russia; Endocrinology Research Centre, Moscow, Russia. Electronic address: yuristafeev@gmail.com. 3. National Medical Research Center for Cardiology, Moscow, Russia; M.V.Lomonosov Moscow State University, Moscow, Russia; Endocrinology Research Centre, Moscow, Russia. 4. Endocrinology Research Centre, Moscow, Russia. 5. Central Clinical Hospital #1 of LLC Russian Railways, Moscow, Russia. 6. National Medical Research Center for Cardiology, Moscow, Russia; Endocrinology Research Centre, Moscow, Russia. 7. National Medical Research Center for Cardiology, Moscow, Russia. 8. National Medical Research Center for Cardiology, Moscow, Russia; M.V.Lomonosov Moscow State University, Moscow, Russia.
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.
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.