Fig. 1: Circadian coordination of liver metabolism.
From: Potential bidirectional communication between the liver and the central circadian clock in MASLD
A circadian pacemaker in the hypothalamic suprachiasmatic nuclei (SCN) is reset by the external light-dark cycle. Through temporal regulation of behavioural functions such as the sleep-wake cycle or feeding-fasting rhythms, endocrine outputs and the autonomic nervous system (ANS), the SCN clock controls the timing of cellular clocks in hepatocytes (and other central and peripheral tissues). At the molecular level, these clocks are comprised of interlocked transcriptional-translational feedback loops (TTFLs) of clock genes and proteins characterised by marked 24-h rhythms in transcriptional activity and protein abundance. In the liver, local clock rhythms and internal (e.g., hormones) and external circadian inputs (e.g., meal schedules) are integrated to generate metabolic clock outputs such as glycogen storage/release, bile acid and triglyceride biosynthesis.
