Low-intensity exercise training improves systolic function of heart during metastatic melanoma-induced cachexia in mice

Cardiac dysfunction often arises during the early stages of cancer cachexia, posing a significant complication of the disease. Physical fitness is commonly recommended in these early stages of cancer cachexia due to its beneficial impacts on various aspects of the condition, including cardiac dysfunction. However, the direct functional impacts of exercise on the heart during cancer cachexia largely remain unexplored. In this study, we induced cancer cachexia in mice using a metastatic B16F10 melanoma model. Concurrently, these mice underwent a physical exercise regimen to investigate its potential role in cardiac function during cachexia. Our findings indicate that exercise training can help prevent metastatic melanoma-induced muscle loss without significant alterations to body and fat weight. Moreover, exercise improved the melanoma-induced decline in ejection fraction and fractional shortening, while also mitigating the increase in high-sensitive cardiac troponin T levels caused by metastatic melanoma in mice. Transcriptome analysis revealed that exercise significantly reversed the transcriptional alterations in the heart induced by melanoma, which were primarily enriched in pathways related to heart contraction. These results suggest that exercise can improve systolic heart function and directly influence the transcriptome of the heart during metastatic melanoma-induced cachexia. Overall design: C57BL/6J male mice (8 weeks old) were divided into the exercise group and the control group. The mice in the exercise group underwent a treadmill running exercise protocol for 5 days per week over a period of 4 weeks. In the first week, the mice were subjected to adaptive training with the following protocol: 6 m/min for 5 min, 9 m/min for 5 min, 12 m/min for 5 min, and 15 m/min for 5 min. Subsequently, for the next 3 weeks, the mice were forced to run at 6 m/min for 5 min and 12 m/min for 35 min. Meanwhile, the mice in the control group were housed in cages without exercise. From the 2nd week of the study, 1×10^5 B16F10 cells were intravenously injected into the mice through the tail vein to induce cancer cachexia