Figure 2.

Circadian Regulation of Hepatic Protein Synthesis and Growth. As illustrated in the figure, hepatic mass reaches a peak at the awake-to-sleep transition, secondary to high protein synthesis rates during the awake period. The latter is promoted by a steady increase in S6K1 activity and BMAL1 phosphorylation, leading to complex formation with eIF3B, eIF4F, and PABP, and subsequent translation initiation. Similarly, rRNA levels increase during the awake period, facilitating ribosome assembly and protein synthesis. Conversely, the increased expression of AMPK and activation of the integrated stress response as the sleep phase progresses attenuates protein synthesis at this time.