Menu

Mouse Livers Grow and Shrink Daily

Feeding-fasting rhythms and light-dark cycles direct regular changes in organ and cell size, as well as ribosome number and protein levels.

May 4, 2017
Abby Olena

Mouse hepatocytes are smallest at the end of the day (left) and largest at the end of the night (right).UELI SCHIBLER, UNIVERSITY OF GENEVASeveral years ago and somewhat by accident, researchers led by Ueli Schibler, now professor emeritus at the University of Geneva in Switzerland, noticed that mouse liver cells are larger toward the end of the night and smaller at the end of the day. In a study published today (May 4) in Cell, the group has not only confirmed that hepatocyte size oscillates daily, but that the entire liver is larger at night when mice are most active. The observed changes in cell and organ size are related to feeding-fasting cycles and are accompanied by increased protein levels and ribosome assembly.

“This is fundamental work,” Carrie Partch of the University of California, Santa Cruz, who was not involved in the study told The Scientist. “The ribosome is this universal machine, and the thought that you have a clock controlling its assembly and tuning when it’s most active is really exciting.”

Schibler and colleagues determined that hepatocyte size swelled throughout night then shrunk during the day. But they only observed this oscillation when they fed the mice at night. When mice were fed during the day, when they are less active, that clear rhythm disappeared, even though the animals ate similar amounts of food.

These cellular cycles appeared to affect the liver as a whole. At the end of the animals’ active period, the livers of night-fed mice were nearly 50 percent larger—as a percentage of total body weight—than after their inactive period. The researchers did not see this pattern in the livers of day-fed mice or in other organs.

A similar pattern emerged when the research team investigated RNA and protein abundances, both of which rose throughout the active phase in night-fed rodents. In contrast, levels of RNA and protein did not change in day-fed mice. DNA levels stayed constant in all animals, indicating that liver cell number does not vary diurnally.

“We think about the liver as having a fairly constant size, but this paper clearly shows that liver size has a circadian rhythm,” said Mitchell Lazar of the University of Pennsylvania who did not participate in the work. “There will be a lot of interest in this phenomenon . . . and what causes it.”

The researchers found that translation efficiency increased midway through the active period in night-fed mice and that ribosomes accumulated in hepatocytes, peaking at the end of the night. Pre-messenger RNA and pre-ribosomal RNA (rRNA) synthesis remained constant over 24 hours, however, suggesting that the rhythm of rRNA accumulation is controlled posttranscriptionally—likely by degradation of ribosomes during the day. Indeed, Schibler’s group found that one rRNA precursor is polyadenylated in a circadian fashion and targeted to the 3’-5’ nuclear exosome complex for destruction.

Surprisingly, when the researchers examined polyadenylation of 18S rRNA precursor in the livers of mice with a gene controlling central circadian rhythms knocked out, the diurnal oscillations didn’t change much. This finding suggests that feeding-fasting cycles play a more important role than the master clock in directing rRNA polyadenylation and ribosome accumulation.

“We have no idea how the light cycle cooperates with the feeding cycle,” Schibler said. “What’s probably more difficult, but also important, is to figure out the function of” these rhythms.

“It’s very likely that this mechanism is also relevant in humans,” he added. Schibler hypothesized that the detoxification function of the liver is influenced by the organ’s circadian rhythms, a possibility that could have implications for the efficacy of drugs processed through the liver. “I think this has a really significant future,” he said. “More people should know about it and more people should work on it.”

See “Circadian Rhythms Influence Treatment Effects

F. Sinturel et al., “Diurnal oscillations in liver mass and cell size accompany ribosome assembly cycles,” Cell, doi:10.1016/j.cell.2017.04.015, 2017.

September 2018

The Muscle Issue

The dynamic tissue reveals its secrets

Marketplace

Sponsored Product Updates

Enabling Genomics-Guided Precision Medicine

Enabling Genomics-Guided Precision Medicine

Download this eBook from Qiagen to learn more about the promise of precision medicine and how QCITM Interpret can help deliver better care with better knowledge.

Best Practices for Sample Preparation and Lipid Extraction from Various Samples

Best Practices for Sample Preparation and Lipid Extraction from Various Samples

Download this white paper from Bertin Technologies to learn how to extract and analyze lipid samples from various models!

Bio-Rad Launches CHT Ceramic Hydroxyapatite XT Media and Nuvia HP-Q Resin for Process Protein Purification

Bio-Rad Launches CHT Ceramic Hydroxyapatite XT Media and Nuvia HP-Q Resin for Process Protein Purification

Bio-Rad Laboratories, Inc. (NYSE: BIO and BIOb), a global leader of life science research and clinical diagnostic products, today announced the launch of two new chromatography media for process protein purification: CHT Ceramic Hydroxyapatite XT Media and Nuvia HP-Q Resin.

Immunophenotypic Analysis of Human Blood Leukocyte Subsets

Immunophenotypic Analysis of Human Blood Leukocyte Subsets

Download this application note from ACEA Biosciences, Inc., to find out how to perform an immunophenotypic analysis of a human blood sample utilizing 13 fluorescent markers using a compact benchtop flow cytometer equipped with 3 lasers!