title: 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 for 10 weeks. MSC-based treatments altered the ratio of adiponectin to leptin and 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 administration not only reduced obesity-associated metabolic syndromes but also reduced body weight and hyperlipidemia, indicating that it is an effective therapy for obesity. Together, our findings revealed the therapeutic potential of MSCs for the treatment of metabolic syndrome.
authors.affiliation: Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hsiao
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Taipei City Hospital, Taipei, Taiwan; Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: DAV47@tpech.gov.tw.
authors.forename: Oscar Kuang-Sheng
authors.initials: OK
authors.lastname: Lee
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism / Q000473:pathology; D054392:Adipokines / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D059305:Diet, High-Fat / Q000009:adverse effects*; D018149:Glucose Intolerance / Q000150:complications / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology / Q000628:therapy; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D008103:Liver Cirrhosis / Q000150:complications / Q000473:pathology / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D024821:Metabolic Syndrome / Q000150:complications* / Q000473:pathology / Q000628:therapy*; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000473:pathology; D009765:Obesity / Q000150:complications* / Q000473:pathology / Q000628:therapy*; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism
chemical_list: D054392:Adipokines; D007328:Insulin; D047492:Peroxisome Proliferator-Activated Receptors