Multi-organ transcriptome atlas of a mouse model of relative energy deficiency in sport

Highlights•We mimic behavior and physiology of REDs in mice using the "exercise-for-food" paradigm•REDs affects extracellular matrix organization in multiple tissues•In females, reproductive organs and muscles are largely affected by energy deficiency•In males, kidneys are largely affected by energy deficiencySummaryInsufficient energy intake to meet energy expenditure demands of physical activity can result in systemic neuroendocrine and metabolic abnormalities in activity-dependent anorexia and relative energy deficiency in sport (REDs). REDs affects >40% of athletes, yet the lack of underlying molecular changes has been a hurdle to have a better understanding of REDs and its treatment. To assess the molecular changes in response to energy deficiency, we implemented the "exercise-for-food" paradigm, in which food reward size is determined by wheel-running activity. By using this paradigm, we replicated several aspects of REDs 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. By integrating transcriptomics of 19 different organs, we provide a comprehensive dataset that will guide future understanding of REDs and may provide important implications for metabolic health and (athletic) performance.Graphical abstract