The impact of cancer cachexia on skeletal muscle gene expression in mice.

Here, we investigate the systematic impact of tumor cachexia on muscle function. From a nutritional supplementation perspective, we examine the influence of fatty acid metabolism on the cachectic state, revealing that dietary supplementation with high-fat diet does not alleviate the muscle and fat dysfunction induced by tumors but instead accelerates muscle degradation. Utilizing RNA-seq transcriptome data from muscle tissue, we identify metabolic abnormalities in muscle during cachexia, with the PDK4 gene being activated initially and showing significant enrichment of PPARd targets. We find that inhibiting PDK4 can mitigate the cachectic state and observe a relationship between the activation of muscle PDK4 and PPARd during cachexia. This is supported by epigenomic data revealing that PDK4 is a transcriptional target gene of PPARd in muscle. Activation and mechanical modulation of PPARd in vivo significantly impact muscle atrophy caused by cachexia. Our research suggests that targeting PPARd could serve as a therapeutic drug target for tumor cachexia. Overall design: Utilize RNA-seq to investigate the transcriptome profile in muscle mediated by C26 cells.