Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

The prevalence of obesity presents a growing obstacle for the medical community worldwide. Calorie rich diets lead to excess energy being deposited in adipose tissue. Two distinct types of adipose exist - white and brown. White adipose tissue stores excess energy, while brown adipose tissue dissipates excess energy in the form of heat. Interestingly, the amount of brown adipose tissue in adults is negatively correlated to body mass index. Brown adipose can provide a natural defence against obesity however it is relatively rare in adults. Stimulating brown adipose would augment resting metabolic rates and increase calorie expenditure in individuals with a caloric rich diet. Recent research in our laboratory has shown that skeletal muscle stem cells (satellite cells) can efficiently form brown adipose. The ability of satellite cells to form brown adipose is through the gene microRNA-133 (miR-133) which acts to reinforce satellite cells forming muscle. Screening of drugs that inhibit miR-133 uncovered Pifithrin-a (PFTa), a reversible p53 inhibitor, to promote brown adipose formation from satellite cells in vitro and in vivo. Experiments suggest that p53 regulates how miR-133 is processed into its active form. We hypothesize that p53 acts to regulate miR-133 processing to increase miR-133 in satellite cells and force them to become muscle. We propose to explore the role of p53 on microRNA processing as well as the ability of PFTa to stimulate brown adipose. Compounds that boost the ability of satellite cells to become brown adipose can be translated into therapeutics to increase basal calorie expenditure and augment weight loss.