Light-phase time-restricted feeding disrupts the muscle clock and insulin sensitivity yet potentially induces muscle fiber remodeling in mice

Abstract

Skeletal muscle plays a critical role in regulating systemic metabolic homeostasis. It has been demonstrated that time-restricted feeding (TRF) during the rest phase can desynchronize the suprachiasmatic nucleus (SCN) and peripheral clocks, thereby increasing the risk of metabolic diseases. However, the impact of dietary timing on the muscle clock and health remains poorly understood. Here, through the analysis of cycling genes and differentially expressed genes in the skeletal muscle transcriptome, we identified disruptions in muscle diurnal rhythms by 2 weeks of light-phase TRF. Furthermore, compared with ad libitum (AL) feeding mice, 2 weeks of light-phase TRF was found to induce insulin resistance, muscle fiber type remodeling, and changes in the expression of muscle growth-related genes, while both light-phase and dark-phase TRF having a limited impact on bone quality relative to AL mice. In summary, our research reveals that the disruption of the skeletal muscle clock may contribute to the abnormal metabolic phenotype resulting from feeding restricted to the inactive period. Additionally, our study provides a comprehensive omics atlas of the diurnal rhythms in skeletal muscle regulated by dietary timing.

Keywords

• Time-restricted feeding
• Skeletal muscle
• Circadian clock
• Muscle fiber remodeling
• Bone mass