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Updated: Sep 9, 2025
06:53
Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
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Daily liver rhythms: Coupling morphological and molecular oscillations.
Ueli Schibler1, Flore Sinturel2, Felix Naef3
1Department of Molecular and Cellular Biology, Sciences III, Geneva CH-1205, Switzerland.
Summary
The liver
Area of Science:
- Chronobiology
- Molecular Biology
- Hepatology
Background:
- Mammalian physiology is governed by a hierarchical circadian timing system, with the suprachiasmatic nucleus (SCN) as the master pacemaker.
- The liver, crucial for metabolic adaptation, exhibits daily rhythms in gene expression, protein synthesis, and detoxification.
- Remarkably, liver mass and hepatocyte morphology oscillate significantly over a 24-hour period.
Purpose of the Study:
- To investigate the mechanisms underlying the diurnal oscillation of liver mass and hepatocyte size.
- To explore the role of the actin cytoskeleton and associated signaling pathways in regulating these circadian rhythms.
- To understand how these cellular changes contribute to the synchronization of liver clocks.
Main Methods:
- Utilized mouse models to study daily fluctuations in liver mass, hepatocyte size, RNA, and protein accumulation.
- Analyzed ribosome content and its correlation with protein synthesis rates.
- Investigated actin cytoskeleton dynamics and its regulation by myocardin-related transcription factors-serum response factor (MRTF-SRF) signaling.
Main Results:
- Liver mass in mice fluctuates by 30–40% daily, accompanied by rhythmic changes in hepatocyte size and global protein/RNA levels.
- Ribosome abundance correlates with liver size, acting as a rate-limiting factor for diurnal protein synthesis.
- Hepatocyte actin cytoskeleton undergoes significant polymerization cycles, with F-actin bundles assembling at night, coinciding with maximal liver size.
Conclusions:
- Circadian rhythms in liver mass are driven by oscillations in hepatocyte size and ribosome content, impacting protein synthesis.
- Actin polymerization cycles in hepatocytes are essential for maintaining cellular robustness during size fluctuations.
- MRTF-SRF signaling, influenced by actin dynamics, plays a role in the circadian transcription of clock genes like Per2, synchronizing liver clocks.
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