Fig. 3: Effects of pharmacological GDF15 and exercise-induced GDF15 on food intake and running behavior.

a, b Effect of single subcutaneous injection of rhGDF15 (8 nmol/kg bw, n = 8) or vehicle (n = 7) on forced treadmill running until exhaustion in mice. c Effect of single subcutaneous injection of rhGDF15 (8 nmol/kg bw, n = 16) or vehicle (n = 16) administered at the onset of the dark cycle on voluntary wheel running distance (2 h, p = 0.0210; 4 h, p = 0.0075; 6 h, p = 0.0036). d, e Effect of daily subcutaneous injections (at the onset of the dark cycle) of rhGDF15 (8 nmol/kg bw, n = 14) or vehicle (n = 14) on voluntary wheel running (day 1, p = 0.0140; day 4, p = 0.0042; day 5, p < 0.001; day 6, p < 0.001; day 7, p < 0.001) and food intake (day 1, p = 0.0032). f, g Effect of single subcutaneous injection of rhGDF15 (8 nmol/kg bw) or vehicle on voluntary wheel running in WT (vehicle n = 6; rhGDF15 n = 6, p = 0.0308) and GFRAL KO (vehicle n = 7; rhGDF15 n = 8) mice. h, i Forced treadmill running to exhaustion in WT (n = 8) and GFRAL KO (n = 8) mice. j Voluntary wheel running distance in WT (n = 12) and GFRAL KO (n = 16) mice k Plasma GDF15 values were measured after forced exercise to exhaustion on treadmill in WT (n = 13) and GFRAL KO (n = 11) mice. l Effect of forced exhaustive treadmill exercise on voluntary wheel running (VWR) in WT (n = 4 sedentary vs. n = 4 forced exercise, p = 0.0261) and GFRAL KO (n = 4 sedentary vs. n = 4 forced exercise, p = 0.0134) mice. m Effect of forced exhaustive treadmill exercise on chow in WT (n = 8) and GFRAL KO (n = 8) mice, and n HFD intake in WT (n = 7) and GFRAL KO (n = 7) mice. Data are presented as mean ±  SEM, *P < 0.05; **P < 0.01; ***P < 0.001. b, g, i, j, l, m, n Two-tailed unpaired t test. c, d, e, k, Repeated measures two-way ANOVA with Bonferroni multiple comparisons test. Source data are provided as a Source Data file.