Depletion of Sirt3 leads to the impairment of adipogenic differentiation and insulin resistance via interfering mitochondrial function of adipose-derived human mesenchymal stem cells

However, the mechanism underlying the metabolic reprogramming and upregulation of mitochondrial function during the differentiation of human mesenchymal stem cells(hMSCs) is largely unclear. Sirt3 has emerged as a sensor in regulating mitochondrial function and antioxidant defence system in cellular response to energy demand or environmental stimuli, but its roles in stem cell differentiation have not been fully understood.

In this study, we used adipose-derived hMSCs (ad-hMSCs) to investigate the role of Sirt3 in adipogenic differentiation and in the function of mature adipocytes. We showed that at the early stage of adipogenic differentiation, Sirt3 upregulation is essential for the activation of biogenesis and bioenergetic function of mitochondria. In addition, we found that induction of Forkhead Box O 3a (FoxO3a), an upstream factor that regulates MnSOD gene transcription, is involved in the upregulation of antioxidant enzymes at the early stage of adipogenic differentiation.