Liver clock: Malalignment and entrainment therapeutics

The mammalian circadian system comprises of a central clock in the suprachiasmatic nucleus (SCN) and peripheral clocks in body tissues and organs i.e. liver clock. Both the central and liver clocks are based on clock genes and their protein products, which regulate circadian rhythms in metabolism, physiology, and behavior by modulating nervous and harmone signaling, including the sympathetic nervous system, fasting and eating behavior. The SCN is primarily entrained by light-dark cycles. Liver clock genes can be influenced by other factors, such as feeding cycles and specific nutrients. Light is the major entraining factor, reaching the SCN through the retina and retinal hypothalamic tract. The liver clock regulates the expression of 10%-15% of the transcriptome, including key metabolic genes. Disruptions in either the central or liver clock can lead to various health issues, including an increased cancer risk and metabolic disorders. Various lifestyle measures, including time-restricted eating, light therapy, temperature control, and melatonin agonists, have been studied for circadian realignment. We reviewed the mechanism of malalignment of central and liver clock genes and existing therapeutic measures for realignment.