FIGURE 5.

Molecular interactions between the clock and metabolic regulators. These physiological relationships can be understood as having 3 main components: metabolic signals, metabolic integrators, and clock integrators. A large number of metabolic signals [e.g., insulin, insulin-like growth factor 1 (IGF-1), amino acids (AA), uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), adenosine monophosphate (AMP), nicotine adenine dinucleotide (NAD⁺), and glucagon] converge on key metabolic signal integrators [e.g., AKT, mammalian target of rapamycin (mTOR), O-GlcNAc transferase (OGT), AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and CREB (cyclic AMP response element-binding protein (CREB)], which in turn regulate the key components of the circadian timekeeping system [i.e., the circadian locomotor output cycles kaput (CLOCK):brain and muscle ARNT-like 1 (BMAL1) heterodimer and the transcriptional repressors cryptochrome (CRY) and period (PER)]. ATP, adenosine triphosphate; GSK3β, glycogen synthase kinase-3β; mTORC1, mammalian target of rapamycin complex 1; O, O-linked glycosylation; P, phosphorylation, S6K, ribosomal protein S6 kinase. Figure was created with BioRender.com, with permission.