Mesenchymal Stem Cells as a Novel Treatment for Obesity Induced Metabolic Dysregulation

Obesity can induce metabolic dysregulation that can result in a cluster of chronic conditions such as hyperglycemia, hyperinsulinemia, dyslipidemia, diabetes and cardiovascular complications. 

The combination of abundance of food and lack of physical activity has led to excessive nutrient storage, introducing major stress on our metabolic pathways and in our bodies, resulting in an increase in the occurrence of diseases originating from metabolic dysfunction. 

Stem cells have a great potential for different clinical applications due to their multipotent capabilities, self-renewal, and differentiation potential. Recently, also their paracrine effects have been found to be one of their main ways of generating the immunomodulatory and regenerative capabilities. 

Adipose-derived mesenchymal stem cells 

Adipose-derived mesenchymal stem cells (ADMSCs) are one source of MSCs obtained by a less invasive method and larger quantities when compared to bone marrow. Previous studies using ADMSCs have demonstrated improvement in insulin resistance in vitro.

In a study published in the International Journal of Obesity, researchers hypothesized that multiple intramuscular injections of ADMSCs may help in normalizing the dysregulated metabolism of diet induced obese animals. 

Study Development and Results  

The researchers use a diet induce obese model in mice that was developed by feeding the mice on a high fat diet. 

The mice were injected with human adipose tissue derived MSCs suspension, conditioned medium and a cell lysate intramuscularly. 

The treated mice exhibited a remarkable decrease in insulin resistance and triglyceride glucose index with a decrease also in LDL levels and IL-6 (a proinflammatory cytokine) when compared to untreated mice in the control group. 

The suspension of ADMSCs also showed improvement in glucose tolerance and reduction in fatty infiltration in the liver and macrophage infiltration in adipose tissue. An increase in protein content in the skeletal muscle of the animals was also observed and it indicates a plausible mechanism of action of the ADMSCs treatment in ameliorating insulin resistance. 

Conclusions

The study evaluated the use of ADMSCs via an intramuscular injection compared to the regular intravenous administration and found that it was a good alternative due to its slow release of their paracrine secretion into the systemic circulation.

The researchers concluded that the use of ADMSCs was effective in reducing the insulin resistance, a decrease in triglyceride and glucose levels, decreased LDL oxidation, while also decreasing inflammatory markers such as IL-6, which opens a new possible therapeutic usage in human subjects by employing autologous or allogeneic MSCs for the management of obesity induced metabolic changes. 

Source:

Shree, N., Venkategowda, S., Venkatranganna, M. V., Datta, I., & Bhonde, R. R. (2019). Human adipose tissue mesenchymal stem cells as a novel treatment modality for correcting obesity induced metabolic dysregulation. International Journal of Obesity. doi:10.1038/s41366-019-0438-5 

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