Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise.
Level 4 - case-series / case-control
Multiple observational human biomarker cohorts combined with mechanistic rodent experiments.
PubMed 33589633 · doi:10.1038/s41467-021-21309-x
What was done
Researchers evaluated circulating growth differentiation factor 15 (GDF15) responses across four independent human studies involving prolonged endurance exercise. They replicated exercise conditions in mouse models to measure tissue-specific *Gdf15* gene expression in the liver, skeletal muscle, and heart muscle, and compared the behavioral effects (food intake and voluntary wheel running) of physiological exercise-induced GDF15 versus pharmacological GDF15 administration via the GDNF family receptor α-like (GFRAL) pathway.
What was found
Prolonged endurance exercise increased circulating GDF15 in humans to concentrations typically seen only in pathophysiological states, with levels correlating with exercise duration. In mice, endurance exercise similarly induced *Gdf15* expression in heart, skeletal muscle, and liver tissue. However, while pharmacological GDF15 suppressed appetite and voluntary running activity via GFRAL, physiological elevation of GDF15 following exercise did not suppress feeding or diminish running motivation. Specific quantitative values (concentrations, effect sizes, and sample sizes) were not reported in the abstract.
Why it matters
These findings distinguish between the pharmacological actions of GDF15 (which induce sickness-like anorectic behaviors) and its physiological release during exercise, showing that natural elevations do not impair energy intake or the drive to exercise.
Limits
The abstract provides no sample sizes, demographic characteristics, or quantitative measurements for the human cohorts or animal experiments. Behavioral and mechanistic divergence between physiological and pharmacological GDF15 was evaluated primarily in rodent models, requiring further confirmation in humans.
Cited by
- supports Injecting animals with GDF15 induces sickness behavior, causing them to hunch into a ball and become inactive.