Fig. 4: Loss of the liver-brain axis reduces body weight and increases energy expenditure in mice fed HFD.

a Schematic representation of the experimental configurations. b Graph showing the changes in body weight between the two groups (n = 16 mice vs. n = 15 mice, p = 0.001). c, d Graphs showing the differences in fat mass and fat-free mass between the two groups (n = 16 mice vs. n = 15 mice; c, p < 0.0001, d, p = 0.03). e Graphs showing no difference in food intake between the two groups (n = 6 mice vs. n = 7 mice). f, g Graphs showing an increase in O2 consumption and CO2 production in the experimental group compared to the control group (n = 6 mice vs. n = 7 mice; f, 24 h, p = 0.0015, light, p = 0.0016, dark, p = 0.0042; g, 24 h, p = 0.0009, light, p = 0.0008, dark, p = 0.003). h Graph showing that the experimental mice exhibited a significant increase in TEE compared with the control group (n = 6 mice vs. n = 7 mice; 24 h, p = 0.003, light, p = 0.003, dark, p = 0.006). i–k Graphs showing the RER and locomotor activity (n = 6 mice vs. n = 7 mice). l ANCOVA analysis showing no difference between the two groups (n = 6 mice vs. n = 7 mice). m Graph showing the changes in body weight of the control and experimental groups (n = 15 mice vs. n = 21 mice; p < 0.0001). n, o Graphs show that the experimental mice exhibited lower fat mass than the controls (n = 15 mice vs. n = 21 mice; p < 0.0001). p Graphs showing no difference in food intake between the two groups (n = 5 mice vs. n = 8 mice). q, r Graph showing an increase in O2 consumption and CO2 production in the experimental group compared to the control group (n = 6 mice vs. n = 5 mice; q, 24 h, p = 0.005, light, p = 0.02, dark, p = 0.002; r, 24 h, p = 0.004, light, p = 0.02, dark, p = 0.003). s Graph showing that the experimental mice displayed a greater TEE than the control group (n = 6 mice vs. n = 5 mice; 24 h, p = 0.002, light, p = 0.006, dark, p = 0.002). t–v Graphs showing no differences in RER or locomotor activity between the groups (n = 6 mice vs. n = 5 mice). w ANCOVA analysis showing a significant difference in the slope between the groups (n = 6 mice vs. n = 5 mice, p = 0.04). Time-course comparisons between groups were analyzed using a two-way repeated-measures analysis of variance with Sidak’s correction for multiple comparisons in b, m. Bar graphs c–k, n–v were analyzed using Two-tailed t-tests. Data are presented as mean values ± SEM. Source data are provided as a Source Data file.