Mesenchymal stromal cell-based therapies reduce obesity and metabolic syndromes induced by a high-fat diet

Abstract

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. To elucidate whether mesenchymal stromal cell (MSC)-based therapies can ameliorate high-fat diet-induced obesity and compare the effectiveness of several methodological approaches, we transplanted human MSCs, MSC-derived brown adipocytes (M-BA), and MSC lysateinto obese mice. All 3 MSC-based treatments improved obesity-associated metabolic syndromes including nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, glucose intolerance, and inflammation in obese mice after repeated administration for10weeks. MSC-based treatments altered the ratio of adiponectin to leptinand regulated the expression of Pparα and Pparγ, which are involved in maintaining energy homeostasis, in major metabolic tissues. Among treatments, M-BA showed the strongest beneficial effect. Importantly, M-BA administrationnot only reduced obesity-associated metabolic syndromes but also reduced body weight and hyperlipidemia, indicating that it is an effective therapyfor obesity. Together, our findings revealed the therapeutic potential of MSCs for the treatment of metabolic syndrome.