Multi-organ transcriptome atlas of a mouse model of relative energy deficiency in sport
The organs hit hardest by under fuelling were the kidney, ovaries, testis and fat, not the muscles.
What this paper showed
How much energy we consume versus expend — and whether we run a surplus or deficit — is a major determinant of health. Among athletes, roughly 60% eat enough to match their training and performance demands, but 40% chronically under-eat relative to their exercise load.
Athletes who train hard without eating enough can develop Relative Energy Deficiency in Sport (REDs) — common in endurance running, cycling, gymnastics, dance, and other sports where leanness is prized, though it appears elsewhere too. Visible signs include lost menstrual periods in females, stress fractures, mood swings, poor sleep, and fatigue. Understanding the molecular and cellular changes behind REDs — organ by organ — could reveal how to manage and reverse it.
The challenge: no molecular studies existed, since tissue or brain biopsies from affected athletes are nearly impossible to obtain. Building a laboratory model of REDs was therefore essential.
Our solution: we built a careful animal model of the condition and profiled gene activity across thousands of genes in many organs simultaneously — producing something closer to a map than a single finding. Tissues seemingly unrelated to running or lifting — kidney, ovaries, testis, and fat — were among the most affected, showing that the disruption is widespread, not confined to muscle.
A related study from the lab examined the brain directly, dissecting 17 regions and tracking gene expression across the day. The most striking result involved the circadian clock: in most regions, the daily rhythm didn't just weaken — it flipped, so genes normally most active at night became most active during the day. This may explain the disturbed sleep seen in both the mice and in REDs athletes.
The practical takeaway: under-fueling isn't a matter of willpower or discipline — it's a physiological injury with a measurable molecular signature. This atlas gives clinicians and coaches something to screen for before a stress fracture occurs.
Broader impact: the findings are a wake-up call for longevity enthusiasts who assume eating less and exercising more is the path to a longer life. In fact, that combination places a heavy toll on the body and brain. People on GLP-1 drugs who continue exercising after reaching their weight goals should pay close attention to their energy balance.
