Fig 1. Description of exercise testing in mice and men.

(A) Schematic description of exercise testing in mice and men. The PXT_m maintains fixed inclination (0°) while speed increases until the test is terminated (Table 1). Training in mice was done on a chamber-enclosed treadmill that allowed it to function as an open circuit indirect calorimeter; and thus, allowed for derivation of VO₂ and VCO₂ values. With the GXT_m (middle) and GXT_h (right), speed and incline simultaneously increased as stages progressed (Table 1). (B) Human and mouse tests used indirect calorimetry to measure VO₂ (solid line) and record VO_2max as well as measure CO₂ (dashed line). Mouse and man tests were randomly selected from WT males (n = 7) and healthy men (n = 6) and used for derivation of all parameters (all data are shown in S1 and S2 Figs). During maximal exercise testing both species have similar responses (RER, lactic acid formation, fuel utilization, O₂ use, heart rate, speed, exhaustion). In the GXT_m, and GXT_h. at VO_2max, VCO₂ intersected or surpassed VO₂, and was a parameter of a positive test (as RER >1.0, middle and right panel). In the PXT_m, VO_2max did not fulfill this criterion (left panel).