CHARACTERIZING THE ROLE OF TRANSIENT RECEPTOR POTENTIAL POLYCYSTIC THREE IN ADIPOCYTE DIFFERENTIATION

Abstract

Obesity is a global epidemics that has not been tackled through traditional prevention techniques, and which deserves attention as it is bound to be one of the biggest strain on countries 0 health budgets in the 21 st century, alongside age-related diseases. This is why novel strategies to treat obesity are currently explored, a most promising one being cell therapy. Due to the recent discovery of brown fat cells, which burn energy through uncoupling of the mitochondrial proton gradient, as opposed to white adipocytes that store energy, extensive work has been carried out to find triggers to brown fat differentiation or white to brown adipocyte conversion. In this study, I characterized a member of the Transient Receptor Potential family, Transient Receptor Potential Polycystic 3 (TRPP3), which has not previously been studied in adipocytes. After having proven that it has a different distribution expression on brown and white adipocytes, we sought to further understand its role, studying it in two different types of stem cells (Stromal vascular fraction (SVF) and mesenchymal stem cells (MSC)). We then did a localization study to see if its emplacement in the cell could help us understand its role better. We sought to co-localize it with the primary cilium, which turned out to be inconclusive and we decided to explore other strategies. We then optimized a silencing protocol to test the effect of silencing TRPP3 von the function and differentiation of cells. We show that reducing TRPP3 expression by the small interfering RNA technique induces a decrease in UCP1 expression, which is characteristic of brown adipocytes. We also observe a decrease in mitochondrial uncoupled respiration, which prove that TRPP3 is necessary for cells to show a brown phenotype. These results therefore show that TRPP3 is necessary for brown fat differentiation. We have therefore identified a novel receptor that could be a promising target for cell therapy against obesity.