Fig. 8.

Fig. 8.

Models of how balance of anabolism and catabolism yields observed muscle growth through interaction of circadian and physical activity-dependent regulation. (A) Circadian muscle growth model. The y axis represents net protein turnover of cellular material, that is, hypertrophy (positive) or atrophy (negative). The x axis represents condition. Observed (and predicted net, from summed colored bars) growth over 12-h period is shown above (numbers in purple). Blue represents anabolism driven by activity. Green represents circadian clock-driven anabolism that is increased during the day. Striped blue and/or green represent the cooperative requirement of the two components, activity and clock, to drive extra daytime growth. Red represents catabolism induced by the circadian clock at night. Yellow represents activity- and clock-independent basal intrinsic anabolism/growth. During a normal LD cycle (Upper), in the presence of activity, muscle growth is fastest in the day, as physical activity cooperates with circadian clock to drive extra daytime anabolism. At night, anabolism reduces and catabolism increases, leading to slower growth, but activity still promotes some growth. In the absence of activity, muscle growth is still faster in the day than at night, although anabolism is reduced. This is because clock still drives nocturnal catabolism, but is insufficient to drive extra daytime anabolism for maximal growth (see striped green surrounded by dashed line). In the absence of a functional clock (Lower), muscle growth in the day is reduced compared with active control, because physical activity alone is insufficient to drive extra anabolism for maximal growth (see striped blue surrounded by dashed line). Growth at night, however, increases as nocturnal catabolism is eliminated. In the absence of activity, muscle growth in the day is unaltered when compared with inactive control. At night, growth again increases, due to the elimination of nocturnal catabolism. Hence, growth is similar between day and night in inactive ΔCLK muscle. Overall, optimal growth and protein turnover is only achieved in active muscle with a functional clock. (B) Proposed mechanisms of clock regulation of metabolism. Gray arrows, daytime pathways; black arrows, nighttime pathways. Note that TORC1 activity is not absolutely required for anabolism/growth; TORC1 activity, however, permits extra anabolism and hence faster growth in the day (blue dashed box), but only when both physical activity and clock are present (green dashed box).