Mouse Model of Relative Energy Deficiency in Sport (REDs)
Description
Insufficient energy intake to meet the energy expenditure demand of physical activity can result in systemic neuroendocrine and metabolic abnormalities in activity-dependent anorexia and Relative Energy Deficiency in Sport (REDs). REDs alone affects >40% of athletes, yet the lack of underlying molecular changes has been a hurdle to have a mechanistic understanding of REDs and its treatment. To assess the molecular mechanisms of how energy balance impacts health, we implemented the ‘exercise-for-food’ paradigm, in which, food reward size is determined by wheel-running activity. By regulating how much wheel-running activity will be rewarded with a food pellet, we mimicked a REDs condition in female and male mice, with high physical activity, and gradually reduced food intake, which results in weight loss, compromised bone health, organ-specific mass changes and altered rest-activity patterns. Here we identify possible mechanisms involved in adaptive changes in physiology and behavior, as a response to low energy availability, by integrating transcriptomics of 19 different metabolic/endocrine organs. Elucidating the mechanisms through which metabolic feedback acts on the neuroendocrine system and metabolic organs may provide important implications for metabolic health and (athletic) performance.