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

GSE246122 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2025/07/03 Platform GPL24247
Summary
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 PPARδ targets. We find that inhibiting PDK4 can mitigate the cachectic state and observe a relationship between the activation of muscle PDK4 and PPARδ during cachexia. This is supported by epigenomic data revealing that PDK4 is a transcriptional target gene of PPARδ in muscle. Activation and mechanical modulation of PPARδ in vivo significantly impact muscle atrophy caused by cachexia. Our research suggests that targeting PPARδ could serve as a therapeutic drug target for tumor cachexia.
Published in
Disrupted methionine cycle triggers muscle atrophy in cancer cachexia through epigenetic regulation of REDD1
Lin K, Wei L, Wang R et al. · Cell metabolism 2025 · PMID 39729999 · doi:10.1016/j.cmet.2024.10.017
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Also filed as BioProject PRJNA1031599 and SRA study SRP468164. Searching any of these in the dataset finder brings you back here.

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