Figure 2

/content/figure/10.1146/annurev-pathmechdis-031521-024831.f2

Figure 2

Circadian clocks and liver physiology. (a) Temporal resetting of the liver clock is illustrated. Information on the day–night cycle is conveyed from the SCN to the liver by humoral signals and innervation, or via rhythmic systemic changes, such as temperature oscillations and SCN-controlled rhythmic glucocorticoid release from the adrenal gland. The liver also receives timing information from patterns of nutrient influx. Reciprocally, liver rhythms affect feeding patterns. Acute events or chronic diseases can result in the deregulation of the molecular clock, and the clock modulates disease outcome. (b) Rhythmic signals either directly activate hepatic target genes (left) or influence the hepatic molecular clock (right). The molecular clock is thought to use autoregulatory mechanisms in which PER:CRY represses the activational complex of BMAL1:CLOCK. This loop mechanism provides rhythmic outputs via NREs, ROREs, and PARREs. Abbreviations: NRE, nuclear receptor response element; PARRE, PARbZip response element; RORE, retinoic acid receptor–related orphan receptor (ROR) response element; SCN, suprachiasmatic nucleus.

pathol/18/1/pm180439.f2_thmb.gif

pathol/18/1/pm180439.f2.gif

Figure 2 Circadian clocks and liver physiology. (a) Temporal resetting of the liver clock is illustrated. Information on the day–night cycle is conveyed from the SCN to the liver by humoral signals and innervation, or via rhythmic systemic changes, such as temperature oscillations and SCN-controlled rhythmic glucocorticoid release from the adrenal gland. The liver also receives timing information from patterns of nutrient influx. Reciprocally, liver rhythms affect feeding patterns. Acute events or chronic diseases can result in the deregulation of the molecular clock, and the clock modulates disease outcome. (b) Rhythmic signals either directly activate hepatic target genes (left) or influence the hepatic molecular clock (right). The molecular clock is thought to use autoregulatory mechanisms in which PER:CRY represses the activational complex of BMAL1:CLOCK. This loop mechanism provides rhythmic outputs via NREs, ROREs, and PARREs. Abbreviations: NRE, nuclear receptor response element; PARRE, PARbZip response element; RORE, retinoic acid receptor–related orphan receptor (ROR) response element; SCN, suprachiasmatic nucleus. Copyright © 2023 by the author(s).

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