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. 2020 Feb 13;11:87. doi: 10.3389/fphys.2020.00087

FIGURE 2.

FIGURE 2

Inflammation and muscle protein turnover. Classical muscle wasting cytokines include TWEAK, TNFα, and IL-6. High concentrations of these cytokines may down-regulate mRNA translation and muscle protein synthesis through inhibition of the PI3K/Akt pathway resulting in GSK3β inhibition of translation and reduced mTOR activation. Increased FOXO nuclear localization along with classical NF-κB and p38 MAPK activity increases transcription of atrophy-related genes (i.e., MuRF1, MAFbx). An imbalance where catabolic signaling exceeds anabolic signaling can lead to muscle atrophy. 4E-BP1, 4E binding protein 1; FOXO, forkhead box O; GSK-3β, glycogen synthase kinase 3β; IGF-1, insulin-like growth factor 1; IL-6, interleukin-6; IRS-1, insulin receptor substrate 1; MAFbx, muscle atrophy F-box; mTOR, mammalian target of rapamycin; MuRF1, muscle ring finger 1; NF-κB, nuclear factor-κB; p38 MAPK, p38 mitogen-activated protein kinase; p70S6K, p70 ribosomal protein S6 kinase; PI3K, phosphoinositide 3-kinase; STAT3, signal transducer and activator of transcription 3; TNFα, tumor necrosis factor-α; TWEAK, TNF-like weak inducer of apoptosis.