Background: Metabolic syndrome (MetS) is a group of signs and symptoms that are associated with a higher risk of Type 2 Diabetes Mellitus (T2DM) and Cardiovascular Diseases (CVDs). The major risk factor for developing MetS is abdominal obesity that is caused by an increase in adipocyte size or number. Adipocyte number multiplication is caused by the differentiation of mesenchymal stem cells into adipose tissue. Numerous studies have evaluated the expression of key transcription factors including PPARG and CEBPB during adipocyte differentiation in murine cells such as 3T3-L1 cell line. In order to comprehend the expression changes during the process of fat accumulation in adipose tissue derived stem cells (ASCs), we compared the expression of DYRK1B, PPARG, and CEBPB in undifferentiated and differentiated ASCs into mature adipocytes between the patient (harboring DYRK1b R102C) and control (healthy individuals) groups. Methods: Gene expression was evaluated on eighth days pre-induction and days 1, 5, and 15 post-induction. The pluripotent capacity of ASCs and the potential for differentiation into adipocytes were confirmed by flow cytometry analysis of surface markers (CD34, CD44, CD105, and CD90), and Oil red O staining, respectively. Expressions of DYRK1B, PPARG, and CEBPB were assessed by RT-PCR in patients' and normal individuals' samples. Results: The expression of DYRK1B kinase and transcription factors (CEBPB and PPARG) are significantly higher in adipose derived stem cells harboring DYRK1b R102C compared to non-carriers on days 5 and 15 during adipocyte differentiation. These proteins may be suitable targets for therapeutic strategies in obesity and obesity related disorders like metabolic syndrome. Furthermore, AZ191 exhibited a potent and selective inhibitory activity toward DYRK1B and CEBPB. Conclusion: CEBPB, PPARA, and DYRK1B contribute to adipogenesis and the development of metabolic syndrome; thus, they can be harnessed in developing therapeutic agents against metabolic syndrome.
MicroRNA-27 (miR-27) Targets Prohibitin and Impairs Adipocyte Differentiation and Mitochondrial Function in Human Adipose-derived Stem Cells