Modulatory effects of mesenchymal stem cells on hepatic mitochondrial reactive oxygen species production in dietary‐induced insulin resistance

Abstract

Mesenchymal stem cells (MSCs) are thought to exert their effects in part by limiting oxidative stress. Of therapeutic interest are the effects of MSCs in insulin resistance, a cause of elevated reactive oxygen species (ROS). In this study, we analyzed the antioxidant activity of MSCs in the dietary‐induced insulin resistant C57BL6 model. Male mice were placed on either a chow (CH) or high fat (HFF, 60% kcal) diet for 18wk. Over a 6d period, mice received two serial injections of either murine serum or MSC enriched serum (2 million cells/injection, separated by 2d) via the tail vein. Analyses included cell survival, glucose tolerance, insulin resistance, respirometry and levels of hepatic mitochondrial ROS production. HFF mice were obese (31±2g vs. 46±3g) and hyperglycemic. Results demonstrated no difference in glucose tolerance or insulin resistance with MSCs. Interestingly, MSCs did not alter the rate of ROS production in CH (H2O2 production: 0.68±0.14 pmol.min−1μg−1 in CH‐MSC vs. 0.63±0.11 pmol.min−1μg−1 in CH‐Serum) but significantly reduced mitochondrial ROS production in HFF (4.85±0.39 vs. 0.72±0.17 pmol.min−1μg−1). In conclusion, short‐term MSC treatment does not impact hyperglycemia but significantly reduces rates of hepatic mitochondrial ROS production. Results invite further exploration into the specific mechanisms by which MSCs reduce ROS in insulin resistant states.Support: HSF, CDA, AIHS