Fig 10. BMAL1- and REV-ERB-dependent programming of muscle metabolism.
Our integration of multiple “–omics” datasets indicates that the muscle clock may modulate diurnal fuel selection in anticipation of the feeding phase by direct BMAL1-dependent activation of genes promoting neutral lipid storage (Dgat2) and metabolic efficiency (Coq10b) while coordinating REV-ERB-mediated repression of a network of genes involved in lipid metabolism (Plin5, Acsl1, Ucp3, Pdk4) and muscle protein turnover (MuRF-1, Atrogin-1, polyubiquitin-C, Snat2). Muscle clock disruption causes loss of BMAL1-dependent activation and REV-ERB-dependent repression of target genes, resulting in a state of metabolic inefficiency characterized by increased lipid mobilization and oxidation and in increased protein turnover. BMAL1, brain and muscle ARNT-like protein 1; HDAC3, histone deacetylase 3; NCoR1, nuclear receptor corepressor 1; RORE, ROR response element.