Grant: Operating Grant

Energy homeostasis is the balanced regulation of fuel intake, storage and expenditure by a person. While a constant supply of energy is required to maintain the basal metabolic rate of the whole individual, energy is also differentially generated and utilized by individual cell types and organs in response to endogenous or exogenous signals specified by various developmental and physiological needs and stimuli. Regulated control of energy production and utilization thus allows the organism to function effectively in a broad range of environmental conditions. On the other hand, disturbance of energy homeostasis over a long period of time can contribute to the etiology of many diseases such as diabetes, obesity, heart failure and even cancer. Imbalance in metabolic homeostasis may originate from nutritional deprivation or overabundance, genetic variations and disorders as well as from gradual loss of efficiency in control systems during the aging process. Consequently, improving our knowledge of how metabolic homeostasis can be maintained through the life of the organism and defining, at the molecular level, control mechanisms that can be manipulated to prevent and treat metabolic-related diseases are of indisputable medical significance. Nuclear hormone receptors play a major role in controlling energy homeostasis, and this grant application is directed at increasing our knowledge of how one sub-family of nuclear receptors, referred to as the estrogen related receptors (ERRs), influences this process in normal physiology and diseases.