Figure 1

The effect of LDM DOX administration and SN co-supplementation on body mass and composition indices, muscle and organ mass. (A) Body mass was measured throughout the experimental timeline and repeated measures analysis performed. A 5% increase in body mass was observed between day 1 and 3 in the VEH mice (*p < 0.05), which was inhibited by DOX such that by day 3, both DOX and DOX + SN mice had a lower body mass compared to VEH (*p < 0.05). Body mass was stable from day 3 to 7 in VEH mice, but declined steadily with DOX treatment from day 5 (*p < 0.05) and DOX + SN treatment from day 3 (*p < 0.05). As such the body mass of DOX and DOX + SN mice was lower compared to VEH at day 5 and 7 (*p < 0.05). Weight loss during this period was actually exacerbated by SN supplementation (^p < 0.05 DOX + SN versus DOX). Body mass declined during the 24 h metabolic cage stay between day 7 and 8 in VEH mice (*p < 0.05) due to participation in voluntary wheel running. Exercise-induced weight loss was not observed in DOX and DOX + SN mice (since they did not run as far as VEH mice) albeit body mass was still lower for these groups compared to VEH mice (*p < 0.05). (B) As defined by a > 5% reduction in body mass displacement relative to the VEH, LDM DOX and DOX + SN treatment induced cachexia (*^p < 0.05). Mirroring body mass changes, both (C) lean and (D) fat mass was significantly lower in DOX and DOX + SN mice compared to VEH mice (*p < 0.05). (E) The mass of extensor digitorum longus (EDL), soleus (SOL), plantaris (PLNT) and tibialis anterior (TA) muscles was significantly reduced by DOX administered alone and in the DOX + SN treatment compared to VEH mice (*p < 0.05). However, when (F) muscle mass was corrected for final body mass (BM), there was no treatment effect observed. Like muscles, organ mass was either lower, or trended to be lower following DOX treatment either alone or in the DOX + SN treatment for each of (G) spleen (SPLN; *p < 0.05 for DOX and DOX + SN compared to VEH), kidneys (KIDS; p = 0.07 DOX versus VEH and *p < 0.05 DOX + SN versus VEH), fat (epididymal and subcutaneous; FAT; *p < 0.05 for DOX versus VEH and p = 0.05 for DOX + SN versus VEH) and liver (LIV; *p < 0.05 for DOX and DOX + SN versus VEH). (H) When corrected for final BM, DOX treatment showed specific targeting of both SPLN (*p < 0.05 for both DOX and DOX + SN versus VEH) and FAT (*p < 0.05 for DOX versus VEH) which was independent of overall body mass reduction . n = 7–8 per group.