Figure 7.

Peripheral sympathetic denervation rescues metabolic abnormalities in tumor-bearing mice. (a) Experimental design. (b) Norepinephrine content in the spleen was reduced in mice that received 6-OHDA, suggesting successful sympathetic nervous system (SNS) ablation (n = 12-14/group, main effect of 6-OHDA F_1,49 = 75.61, p < 0.0001). (c) 6-OHDA treatment normalized blood glucose concentrations in tumor-bearing mice (n = 14- 15/group; main effect of tumor F_1,55 = 6.923, p = 0.011; main effect of 6-OHDA F_1,55 = 47.86 p < 0.0001; interaction F_1,55 = 7.58, p = 0.008). 6-OHDA normalized (d) liver ldha expression (n = 14-15/group; main effect of tumor F_1,54 = 16.73, p = 0.0001; main effect of 6-OHDA F_1,54 = 10.51, p = 0.002; interaction F_1,54 = 33.48, p < 0.0001) (e) liver gck (15/group; main effect of tumor: F_1,56 = 19.97, p < 0.0001; main effect of 6-OHDA F_1,56 = 37.54, p < 0.0001), (f) pklr (n = 15/group; main effect of 6-OHDA F_1,56 = 11.2, p = 0.0014). (g) g6pc (no change), (h) slc2a4 (n = 14- 15/group; main effect of 6-OHDA F_1,53 = 70.04, p < 0.0001), (i) pck1 (no change) (all 6-OHDA data collected at ZT 6) (2-way ANOVA † = main effect of 6-OHDA, * = main effect of tumor, § = interaction; different letters indicate p < 0.05 difference with Tukey’s post-hoc test). Data that did not meet requirements for ANOVA were log2- transformed. In a separate cohort, tumor-bearing mice had altered satiety hormonal signaling. (j) serum acyl-ghrelin concentrations were unchanged between groups (n = 18-19/group), (k) however tumor-bearing mice increased feeding responses to exogenous ghrelin after a 14 hour fast (n = 14-15/group) ZT 14 injection; main effect of ghrelin F_1,55 = 15.67, p = 0.0002; main effect of tumor status F_1,55 = 5.738, p = 0.02; † = main effect of tumor, * = main effect of ghrelin). Tumor bearing mice showed reduced serum leptin concentrations during the day (n = 15/group; ZT 7 t = 5.54, p < 0.0001)