Mesenchymal stem cells (MSCs) are often considered to be a good source for the development of regenerative medicine. Previously, we reported that tonsil-derived MSC conditioned medium (T-MSC CM) produces visceral fat reducing effects. As reduced visceral adiposity is closely associated with an increase in circulating adiponectin, the present study investigated the effects of T-MSC CM on adiponectin production. T-MSC CM was collected from previously isolated and characterized T-MSCs and injected into senescence-accelerated mouse prone 6 mice, which exhibit characteristics of aging and obesity. The results demonstrated a reduction in mouse weight and epididymal adipose tissue (eAT) mass following injection of T-MSC CM. Significant increases in adiponectin expression in the eAT, and total and high molecular weight (HMW) adiponectin in the circulation were observed in the T-MSC CM-injected mice compared with control mice using reverse transcription-quantitative polymerase chain reaction, western blot analysis and ELISA. In 3T3-L1 adipocytes, T-MSC CM treatment increased adiponectin secretion and multimerization, as detected using western blotting under non-reducing and non-heat-denaturing conditions. Furthermore, glucose oxidase was used to induce oxidative stress in 3T3-L1 adipocytes and it was observed that T-MSC CM reduced reactive oxygen species production and the expression of certain oxidative stress markers. In addition, the results also demonstrated that the production of HMW adiponectin was increased, which indicates that T-MSC CM may enhance adiponectin multimerization via amelioration of oxidative stress. Further studies are required to elucidate anti-oxidant molecules secreted from T-MSCs, and these results highlight the potential therapeutic relevance of T-MSC CM for the treatment of obesity or obesity-associated diseases.
Bibliographical noteFunding Information:
This study was supported by the Bio & Medical Technology Development Program of the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (grant no. 2012M3A9C6049823), Ministry of Education (grant no. 2016R1A6A3A11933360) and Intramural Research Promotion Grants from Ewha Womans University School of Medicine (Seoul, Korea).
- 3T3-L1 adipocyte
- High molecular weight adiponectin
- Oxidative stress
- Senescence-accelerated mouse prone 6
- Tonsil-derived mesenchymal stem cells