Grant: Discovery Grants Program - Individual

REGULATION OF WHOLE-BODY ENERGY HOMEOSTASISThis 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 experiments to elucidate the contribution of major organs that integrate lean body mass (LBM) to whole-body energy metabolism. It mainly focuses on understanding the energy-sparing and energy-dissipating mechanisms that are activated under conditions of altered food intake (energy deficit and surplus) and 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. The main objectives are: a) to determine the time-course effects of food restriction and energy surplus, as well as of exercise-mediated increased energy expenditure and reduced fat mass on 24-hour whole-body energy balance; b) To assess acute and chronic adaptations in metabolic partitioning in skeletal muscle, liver, kidney, and heart to food restriction and energy surplus, as well as to exercise-mediated increased energy expenditure; and c) to determine the effects of acute and chronic energy restriction and surplus and exercise-mediated increased energy expenditure on the hypothalamus-pituitary-thyroid (HPT) axis. Methodology: For in vivo experiments, male Wistar rats will be exposed to caloric restriction, caloric surplus (high-fat diet), and exercise-mediated increased energy expenditure (treadmill endurance training). For in vitro experiments, tissues isolated from rats exposed to the various conditions described above will be used either for incubation and determination of glucose and lipid metabolism or for the analysis of gene expression and signaling mechanisms involved in the regulation of these pathways.