Regulation of whole-body energy homeostasis

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This research program focuses on developing a greater understanding of the basic fundamental physiological and molecular mechanisms involved in the regulation of glucose and fat metabolism and energy balance at the cell, tissue, and whole-body levels. It includes experiments using living organisms (rats and mice) and isolated cells and tissues designed to elucidate how endocrine, molecular, and physiological mechanisms affect energy storage and consumption in major organs that regulate whole-body energy metabolism. It focuses on understanding the energy-sparing and energy-consuming mechanisms that are activated under conditions of altered adiposity (gain and loss of fat) under conditions of thermic stress (cold), chronic endurance exercise, and manipulation of dietary composition. This is important because the ability to store and conserve energy is essential for survival and reproductive capacity, and it is affected by diet, exercise, environmental changes, and hormonal secretions. Furthermore, this research program will advance our understanding of the molecular and physiological mechanisms that regulate adiposity and substrate partitioning in skeletal muscle, liver, and white and brown adipose tissues. Male and female rodents (rats and genetically modified mice) will be exposed to the following interventions: 1) a high-fat sucrose-enriched diet to promote adipose tissue growth, 2) endurance training using treadmill running to increased energy expenditure and reduce adiposity, 3) cold acclimation to activate brown fat thermogenesis and induce white adipose tissue browning, and 4) a ketogenic diet to alter cellular and whole-body substrate partitioning. Indirect calorimetry is used to assess 24h whole-body energy expenditure, metabolic partitioning, and alterations in resting metabolic rate. Time course analysis of body composition (lean mass and adiposity) are performed using animal dissection techniques and/or the microCT system that performs imaging similar to CT scans for humans, but it is designed specifically for mice and rats. Also, isolated cells and tissues from rodents exposed to the various conditions described above are used for incubation and determination of glucose and lipid metabolism using radiolabeled tracers, for assessment of oxygen consumption (by using the Oroboros Oxygraph2k instrument), and for the analysis of gene expression (mRNA expression by Realtime PCR) and signalling mechanisms (content and phosphorylation of specific proteins by Western blot) involved in the regulation of pathways that control cell, tissue, and whole-body energy metabolism. This research is important as it will expand our knowledge in fields of adipose tissue biology, body weight regulation, nutrition, and exercise physiology and provide opportunities for specialized training of students. Thus, this research will advance basic translational science in Canada and increase the qualification and competitiveness of Canadian scientists.