Hepatic signal transducer and activator of transcription-3 signalling drives early-stage pancreatic cancer cachexia via suppressed ketogenesis.
Paige C Arneson-WissinkHeike MendezKatherine PelzJessica DickieAlexandra Q BartlettBeth L WorleyStephanie M KrasnowRobert EilAaron J GrossbergPublished in: Journal of cachexia, sarcopenia and muscle (2024)
In early PDAC cachexia, muscle vulnerability to wasting is dependent on inflammation-driven metabolic reprogramming in the liver. PDAC suppresses lipid β-oxidation and impairs ketogenesis in the liver, which is reversed in genetically modified mouse models deficient in IL-6/STAT3 signalling or through ketogenic diet supplementation. This work establishes a direct link between skeletal muscle homeostasis and hepatic metabolism. Dietary and anti-inflammatory interventions that restore ketogenesis may be a viable preventative approach for pre-cachectic patients with pancreatic cancer.
Keyphrases
- skeletal muscle
- early stage
- anti inflammatory
- physical activity
- mouse model
- oxidative stress
- insulin resistance
- climate change
- signaling pathway
- weight loss
- cell proliferation
- transcription factor
- nuclear factor
- hydrogen peroxide
- fatty acid
- adipose tissue
- metabolic syndrome
- immune response
- inflammatory response
- rectal cancer
- neoadjuvant chemotherapy