Grant: Project Grant

Cardiometabolic disease and Diabetes: Cardiometabolic diseases (CMDs) are related ailments including obesity, high cholesterol, blood sugar, and blood pressure, that significantly increase risk of type 2 diabetes (T2DM). CMDs affect >20% of Canadians and preserving muscle health in patients is of utmost importance. Unfortunately, diet, exercise, and medications don't address underlying genetic and molecular factors contributing to T2DM. CMD rates change drastically when separated by ancestry; some patient groups have increased incidence/mortality, even when controlling for age, sex, income, etc. and genome-wide studies have yet to explain this. Mitochondria and CMD: Mitochondria, components of all our cells that generate energy from our food ("the powerhouse of the cell"), have their own DNA (mtDNA), and this "signature" varies with ancestry. Our group has previously described the role of mtDNA signature in susceptibility to obesity, but how mtDNA causes differing disease profiles is unknown. We think: CMD exhibits ancestral differences that are determined by mtDNA signature. How we will prove this: We will observe how CMD develops in mice with different mtDNA signatures by tracking the onset and progression over 18 weeks and measuring molecular changes occurring throughout, with the goal of identifying a "fingerprint of CMD" that can be detected in a blood sample. Relevance: We aim to translate these findings to patients; mapping an CMD fingerprint specific to a patient's mtDNA signature will improve early intervention for high-risk groups, help address healthcare inequalities and provide new tools to advance personalized care for CMDs and T2DM.