Rhythmic Insulin Induced by Eating During the Active Phase Promotes Skeletal Muscle Growth via Synchronizing Mitochondrial Energy Supply Rhythm and Cell Cycle.

Food intake during the inactive period disrupts the metabolic rhythm of skeletal muscle. Energy metabolism is closely related to muscle growth. However, the impact of eating time on skeletal muscle growth remains unclear. In this study, nocturnal rabbits were subjected to day-restricted feeding (DRF) and night-restricted feeding (NRF), and it was found that DRF disrupted insulin rhythm, whereas NRF enhanced insulin rhythm and promoted skeletal muscle growth. The pathway analyzed by RNA-seq found that circadian rhythm and pancreatic secretion pathways were enriched in Tibialis anterior muscle. Mechanistically, we found that rhythmic insulin couples mitochondrial oxidative phosphorylation rhythm with mitochondrial fission-fusion rhythm by altering BMAL1 phase, which synchronized mitochondrial ATP production rhythm with the G1/S phase progression of the cell cycle and thus promoted myoblast proliferation. Our findings suggest that food intake during the active phase enhances insulin-mediated mitochondrial energy supply rhythm, thereby promoting skeletal muscle growth. This study provides a new perspective for guiding a healthy diet for growth in children and farm animals.