The potential of brown fat explored with mathematical modeling

The potential of browning of white adipocytes as a treatment for obesity and related diseases have recently been acknowledged. The search for new drugs/pathways involved in browning is therefore interesting. In collaboration with AstraZeneca, this project analyzed the mitochondrial functionality of adipocytes that have been treated to become brown. We used mechanistic models to test hypotheses and we used model predictions to design new experiments.

 
In this project, we showed that treatment with the agents Rosi (rosiglitazone) and BMP4 (bone morpogenic protein 4) both induce browning of fat cells with increased uncoupled respiration. However, BMP4-treated cells do not contain detectable levels of the mitochondrial uncoupling protein (UCP1), known to be involved in uncoupled respiration in brown and beige fat cells. To unravel this intricate situation, we used mathematical models, and found a new mechanism of browning of potential interest for new treatments within obesity.

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