Grant: Discovery Grants Program - Individual

This ongoing research program is designed to develop a greater understanding of the basic fundamental physiological and molecular mechanisms involved in the regulation of substrate partitioning and energy balance at the cell, tissue, and whole-body levels. It includes in vivo and in vitro experimental approaches designed to elucidate how endocrine, molecular, and physiological mechanisms that affect energy storage and dissipation in major organs that regulate whole-body energy homeostasis. It focuses on understanding the energy-sparing and energy-dissipating mechanisms that are activated under conditions of altered food intake (energy deficit and surplus) and increased energy expenditure (chronic endurance exercise). 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, and hormonal secretions. Furthermore, this research program will advance our understanding of the mechanisms that regulate adiposity and its potential association with the development of metabolic disorders such as obesity and type 2 diabetes. For in vivo studies, rodents are exposed to caloric restriction, caloric surplus (high-fat diet), exercise-mediated increased energy expenditure (treadmill endurance training), as well as to acute and chronic treatment with pharmacological agents that affect cellular and whole-body substrate partitioning. Indirect calorimetry is used to assess 24-h whole-body energy expenditure, metabolic partitioning, and alterations in resting metabolic rate. Time-course analysis of body composition (lean body mass and fat mass) are performed using the microCT system that performs imaging similar to CT scans for humans, but is designed specifically for mice and rats. For in vitro studies, 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 Oxygraph-2k instrument), and for the analysis of gene expression (mRNA expression by Real-time PCR) and signaling 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.