Human adipose tissue mesenchymal stem cells as a novel treatment modality for correcting obesity induced metabolic dysregulation.

Abstract

Obesity induced metabolic dysregulation results in cluster of chronic conditions mainly hyperglycemia, hyperinsulinemia, dyslipidemia, diabetes, cardiovascular complications and insulin resistance. To investigate the effect of i.m. injection of human adipose tissue derived mesenchymal stem cells and its secretome in correcting obesity induced metabolic dysregulation in high fat diet fed obese model of mice and understand its mechanism of action. We injected human adipose tissue derived mesenchymal stem cells (ADMSCs) suspension (CS), conditioned medium (CM) and the cell lysate (CL) intramuscularly in high fat diet (HFD)-induced C57BL/6 mice. Metformin was used as a positive control. ADMSCs were traced in vivo for its bio distribution after injection at different time points. ADMSCs-treated mice exhibited remarkable decrease in insulin resistance as quantified by HOMA-IR and triglyceride glucose index with concomitant decrease in oxidized LDL and IL6 as compared with the untreated control. CS injection showed improvement in glucose tolerance and reduction in fatty infiltration in the liver, macrophage infiltration in adipose and hypertrophy of the islets resulting from HFD. Upregulation of miRNA-206, MyoD and increase in protein content of the skeletal muscle in CS-treated mice indicates plausible mechanism of action of ADMSCs treatment in ameliorating IR in HFD mice. Of all the three treatments, CS was found to be the best. ADMSCs were found to have migrated to different organs in order to bring about the correction in dysregulated metabolism induced by obesity. Our results open up a novel treatment modality for possible therapeutic usage in human subjects by employing autologous or allogeneic ADMSCs for the better management of obesity induced metabolic dysregulation.