Schematic illustration of Z526's effects on cancer-associated cachexia. (IMAGE)
Caption
In cancer-associated cachexia, elevated TNF-α and IL-6 exacerbate muscle and fat loss by regulating multiple metabolic signaling pathways, which could be ameliorated by Z526's suppression of NF-κB signaling and oxidative stress. In cachectic muscle, Z526 alleviates muscle atrophy by promoting protein synthesis via AKT/mTOR signaling and reducing protein degradation via STAT-3/MAFbx, NF-kB/MAFbx, and MAPK/MAFbx; in cachectic fat, Z526 mitigates fat loss by suppressing MAPK/HSL and NF-kB/HSL to reduce adipose degradation and inhibiting AMPKα/UCP1 to decrease adipose browning. AKT, protein kinase B; AMPKα, catalytic alpha (α) subunit of serine/threonine kinase adenosine monophosphate-activated protein kinase; HSL, hormone-sensitive lipase; IL-6, interleukin 6; MAFbx, muscle atrophy F-box; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; NF-kB, nuclear factor-kappa B; STAT-3, signal transducer and activator of transcription 3; TNF-α, tumor necrosis factor α; UCP1, uncoupling protein 1.
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The authors
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CC BY-NC-ND