Funding agencies: This study was supported by the Alberta Diabetes Research Foundation (Edmonton, AB) and MitoCanada.
Enhanced stem cell engraftment and modulation of hepatic reactive oxygen species production in diet-induced obesity
Article first published online: 23 SEP 2013
© 2013 The Obesity Society
Volume 22, Issue 3, pages 721–729, March 2014
How to Cite
Nyamandi, V. Z., Johnsen, V. L., Hughey, C. C., Hittel, D. S., Khan, A., Newell, C. and Shearer, J. (2014), Enhanced stem cell engraftment and modulation of hepatic reactive oxygen species production in diet-induced obesity. Obesity, 22: 721–729. doi: 10.1002/oby.20580
Disclosure: The authors have no conflicts of interest to declare.
Author Contribution: V.Z.N., V.L.J., C.C.H., D.S.H., and J.S. did the conception and design of the experiments. V.Z.N., C.N., V.L.J., C.C.H., D.S.H., and J.S. performed the experiments and collected data. V.Z.N. and C.C.H. analyzed the data. V.Z.N., J.S., and C.N. drafted the manuscript. D.S.H., A.K., and J.S. reviewed and edited the manuscript. J.S. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
- Issue published online: 5 MAR 2014
- Article first published online: 23 SEP 2013
- Accepted manuscript online: 26 JUL 2013 08:16PM EST
- Manuscript Accepted: 22 JUL 2013
- Manuscript Revised: 16 JUL 2013
- Manuscript Received: 27 MAY 2013
The impact of dietary-induced obesity (DIO) on stem cell engraftment and the respective therapeutic potential of stem cell engraftment in DIO have not been reported. The objectives of this study were to examine the impact of DIO on the survival and efficacy of intravenous bone marrow-derived mesenchymal stem cell (MSC) administration in the conscious C57BL/6 mouse.
Male mice consumed either a chow (CH) or high fat (HF, 60% kcal) diet for 18 weeks and were subsequently treated with MSC over a 6-day period. Key measurements included tissue-specific cell engraftment, glucose and insulin sensitivity, inflammation, and oxidative stress.
MSC administration had no effect on inflammatory markers, glucose, or insulin sensitivity. DIO mice showed increases in MSC engraftment in multiple tissues compared with their CH counterparts. Engraftment was increased in the HF liver where MSC administration attenuated DIO-induced oxidative stress. These liver-specific alterations in HF-MSC were associated with increases in stanniocalcin-1 (STC1) and uncoupling protein 2 (UCP2), which contribute to cell survival and modulate mitochondrial bioenergetics.
Results suggest that MSC administration in DIO promotes engraftment and mitigates hepatic oxidative stress. These data invite further exploration into the therapeutic potential of stem cells for the treatment of DIO oxidative stress in the liver.