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

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Abstract

Objective

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.

Subjects

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.

Results

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.

Conclusion

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.

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Acknowledgements

Authors wish to thank Dr. Anandhwardhan Hardikar, University of Sydney, Australia for his technical inputs in the miRNA study. We would also like to thank ACTREC, Tata memorial Hospital, Mumbai, India for carrying out the LCMS/MS study.

Author contributions

NS and SV carried out the experimental work. MVV suggested for experimental design and provided the animal facility. ID designed the in vivo tracking of the cells and provided the facility for the same. RRB designed the experiment, executed the experimental work and wrote the paper.

Author information

Authors and Affiliations

  1. School of Regenerative Medicine, Manipal Academy of Higher Education, Bangalore, India

    Nitya Shree & Ramesh R. Bhonde

  2. Department of Biotechnology, Jain University, Bangalore, India

    Sunil Venkategowda

  3. Connexios Life Sciences Pvt. Ltd., Bangalore, India

    M. V. Venkatranganna

  4. Department of Biophysics, NIMHANS, Bangalore, India

    Indrani Datta

  5. Dr. D.Y. Patil Vidyapeeth, Pune, India

    Ramesh R. Bhonde

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  1. Nitya Shree
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  2. Sunil Venkategowda
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  5. Ramesh R. Bhonde
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Correspondence to Ramesh R. Bhonde.

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Shree, N., Venkategowda, S., Venkatranganna, M.V. et al. Human adipose tissue mesenchymal stem cells as a novel treatment modality for correcting obesity induced metabolic dysregulation. Int J Obes 43, 2107–2118 (2019). https://doi.org/10.1038/s41366-019-0438-5

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