Oxaliplatin induces cancer-like cachexia through distinct transcriptional pathways in mouse muscle and adipose depots

Oxaliplatin, a platinum-based chemotherapeutic, is a common, first-line treatment for metastatic colorectal and other malignancies that result in cancer cachexia. Yet, it is unknown whether oxaliplatin contributes to these effects independently of cancer.

To reveal its role in cachexia development, we administered a chronic human-equivalent oxaliplatin dose to non-tumor-bearing C57BL/6 mice. Daily activity, muscle wasting, fat depletion, and metabolic parameters were monitored through metabolic cages and echo-MRI measurements followed by postmortem muscle and fat tissue histology and bulk RNA seq. Our results show that a high accumulative oxaliplatin dose of 80 mg/kg leads to cachexia-like symptoms, characterized by severe loss of body mass, decreased food intake, diminished ambulatory activity accompanied by lowered core body temperature, decreased skeletal muscle mass, and loss of adipose tissue.