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Background and objectives: It has been suggested that irisin and fibronectin type III domain-containing protein 5 (FNDC5) can increase energy expenditure, promote weight loss and improve insulin resistance in diabetic patients by affecting white and brown adipose tissues. In this study, we investigate effect of adipose tissue-derived stem cell transplantation and six weeks of aerobic exercise on FNDC5 and irisin levels in streptozotocin-induced diabetic rats.
Methods: Forty-eight rats (weighing 220-240 g and aged nine weeks) were divided into six groups of control, sham, diabetes control, diabetes + exercise, diabetes + stem cell and diabetes+ exercise + stem cell. The exercise group ran on running wheel at intensity of 60-70% VO₂max, five days a week for six weeks. Next, 1.56 × 10⁶ stem cells extracted from human adipose tissue were injected into the tail vein of streptozotocin-induced diabetic rats. Finally, FNDC5 and irisin plasma levels of the mice were measured using enzyme-linked immunosorbent assay kits.  
Results: FNDC5 and irisin levels reduced significantly in the diabetes control group (P=0.0001). FNDC5 levels in the diabetes + exercise + stem cell and the exercise group increased significantly compared to the diabetes control group (P=0.0001). The irisin level in the diabetes + stem cell + exercise group, exercise group and stem cell group increased significantly compared to the diabetes control group (P=0.0001).  
Conclusion: The results indicate that aerobic exercise program and stem cell therapy alone and combined can significantly increase plasma irisin levels. Given the favorable effects of adipose tissue-derived stem cell injection and aerobic exercise on FNDC5 and irisin levels, this strategy could be further evaluated in coping with the adverse effects of diabetes on metabolism and aging