Obesity is an alarming global health problem that results in multiaspect metabolic syndromes in both genders and most age groups. The lack of effective therapies for obesity and its associated metabolic syndrome is an urgent societal issue. We found that repeated transplantation of human MSCs, MSC-derived brown adipocytes (M-BA), and MSC lysate into obese mice are able to improve obesity-associated metabolic syndromes including nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, glucose intolerance, and inflammation in obese mice. In addition, MSC-based treatments altered the ratio of adiponectin to leptin to maintaining energy homeostasis, in major metabolic tissues. Together, MSCs and their derivatives have great potential to treat metabolic syndrome. (Lee CW et al. Transl Res. 2017 Apr.)