Fig. 7: Suppression of Il6ra expression in AP neurons attenuates cachexia and reduces the hyperactivity in the AP network in the C26 cancer model.

a A schematic of the experimental procedure. When one animal in the lacZ sgRNA (control) group became cachectic, that animal and a randomly selected animal in the Il6ra sgRNA-4 group were euthanized to check Fos expression and other phenotypes. b Average bodyweight normalized to that on day -5 (F(1,36) = 10.45, P = 0.0026, **P = 0.0072, two-way repeated-measures (RM) ANOVA with Sidak’s post hoc test, lacZ sgRNA group, n = 4 mice, Il6ra sgRNA-4 group, n = 4 mice). c Inguinal fat mass (t = 3.941, **P = 0.0079, t test). d Quadriceps muscle mass (t = 5.26, **P = 0.0019, t test). e, f Normalized cumulative food (e) and water (f) intake of the mice before being euthanized (food, F(1, 36) = 1.83, P = 0.18; water, F(1, 36) = 1.824, P = 0.19; two-way RM ANOVA with Sidak’s post hoc test). g, h Tumor (g) and spleen (h) mass of the mice (tumor, t = 0.444, P = 0.6725; spleen, t = 0.898, P = 0.404; t test). i Confocal immunochemical images showing Fos expression in different brain areas in representative mice of the two groups. j Quantification of Fos⁺ cells in different brain areas (AP, t = 4.617, **P = 0.0036; NTS, t = 1.5, P = 0.18; PBN, t = 2.849, *P = 0.029; PVN, t = 5.332, **P = 0.0018; CeA, t = 0.5267, P = 0.617; BNST, t = 0.27, P = 0.796; t test with false discovery rate adjusted). AP, area postrema; NTS, nucleus tractus solitarii; PBN, parabrachial nucleus; PVN, paraventricular nucleus of hypothalamus; CeA, central amygdala; BNST, bed nucleus of the stria terminalis. Data in b-h & j are presented as mean ± s.e.m. Source data are provided as a Source Data file.