Grant: Doctoral: Vanier Canada Graduate Scholarships

According to the World Health Organization, obesity has more than doubled globally since 1980, affecting over 1.5 billion adults. In Canada, statistics reveal that in 2008, over 8 million people suffered from obesity, with estimated costs exceeding $4.6 billion. Given that obesity is extremely complex and a major risk factor for other conditions such as cardiovascular diseases, diabetes, diseases of the joints, and some cancers (including endometrial, breast, and colon), it is clear that it constitutes an important area of research. As such, much effort has been put into elucidating the genetic predictors of obesity in order to contribute to its prevention and treatment. This is the basis from which the proposed project evolves. It was previously established that deficiency of a certain molecule in the "powerplants" of cells, named Coenzyme Q10, increases the risk for obesity. One of the genes that is essential for cellular production of Coenzyme Q10 is called Prenyl Diphosphate Synthase Subunit 1 (PDSS1). Never before has anyone linked this gene with obesity and we now have preliminary evidence from genetic studies of over 2000 patient records that suggest PDSS1's importance. Thus, we will investigate the role of PDSS1 in the development of obesity and as a possible target for treatment. Using cultured model cells, we will reduce levels of PDSS1 and evaluate cellular responses. At the clinical level, we will compare PDSS1 levels in obese and lean individuals in order to determine expression patterns. We expect that the PDSS1 gene will be defective in some obese individuals, and our experimental work may demonstrate that we can reverse this defect with CoQ10 supplementation. Ultimately, this translational project will yield an improved understanding of the role of energy expenditure mechanisms in the development of obesity and will also allow the development of novel therapeutic and pharmaceutical strategies to improve weight loss success in clinical programs.