The 2012 CDA-CIHR INMD young investigator award lecture: dysfunction of adipose tissues and the mechanisms of ectopic fat deposition in type 2 diabetes.

Ectopic fat deposition in skeletal muscles, liver, heart, and other tissues has been closely linked with the development of lean tissues' insulin resistance and progression toward type 2 diabetes mellitus. Mechanisms of overexposure of these tissues to fatty acids include increased de novo lipogenesis, impaired fatty acid oxidation and increased fatty acid flux to these organs. White adipose tissues are the main organs responsible for the regulation of circulating fatty acids. It has been clearly demonstrated that pre-diabetes individuals and individuals with diabetes display impaired adipose tissue dietary fatty acid storage that may lead to increased circulating flux and exaggerated lean tissue fatty acid exposure. Additionally, brown adipose tissue depots are less metabolically active in individuals with type 2 diabetes. We have developed a series of novel in vivo investigative tools using positron emission tomography to comprehensively assess postprandial interorgan fatty acid partitioning and white and brown adipose tissue metabolism in subjects with pre-diabetes and type 2 diabetes. Our findings shed new lights into the sophisticated mechanisms that regulate fatty acid partitioning and energy homeostasis during the development of type 2 diabetes. New links between abnormal dietary fatty acid metabolism and early myocardial metabolic and functional defects are now being uncovered in humans with the hope to find novel ways to predict and avoid the devastating complications of diabetes.