Path analysis reveals that corticosterone mediates gluconeogenesis from fat-derived substrates during acute stress in songbirds

Glucocorticoids (e.g., corticosterone or CORT in birds) mobilize energy reserves during stress to aid survival. Stress liberates glucose (GLU) by glycogenolysis, but with glycogen depletion, gluconeogenesis of fat and protein sources predominates. Songbirds have higher metabolic rates and GLU concentrations than mammals and likely rely more on fat and protein stores during stress. We tested this hypothesis in four songbird species using path analysis to model the interrelationships between CORT and energy metabolites both at baseline and after acute stress. Individuals in better condition had higher triglyceride and CORT levels at baseline than individuals in poor body condition, and these differences became more pronounced with stress. Free CORT (the fraction unbound to circulating proteins) was associated with more GLU and free glycerol at baseline, but the former relationship was lost after acute stress. This suggests a shift from a combination of glycogenolysis and gluconeogenesis to solely the latter with acute stress. Glucose levels were also associated with uric acid indicating that birds obtain GLU during stress from gluconeogenesis of mostly fat-derived substrates. This provides a previously elusive functional link between body condition and the stress response, and suggests songbirds are more susceptible to stress challenges during energy-limiting conditions than mammals.