Liver size grows by half during waking hours

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Mouse liver cells: The size of the hepatocytes reaches its maximum at the end of the night (left) and its minimum at the end of the day (right).
Credit: Ueli Schibler, UNIGE

The increased risks of insomnia, anxiety and depression associated with working at night have been well established, but now it seems that confounding the body’s normal circadian rhythms might also have serious implications for liver function.

Mouse-based research from the University of Geneva in Switzerland has established that the liver increases in size by almost 50 per cent when the animals are active and feeding according to their normal, nocturnal circadian cycle, shrinking again during sleep.

When the circadian rhythm is reversed, however, putting the mice into a diurnal feeding cycle, the liver fluctuation disappears.

The research, published in the journal Cell, and led by molecular biologist Ueli Schibler, found that individual liver cells gradually increase in size during the mice’s normal feeding and activity period.

As feeding progressed, each cell accelerated its production of ribosomes, the organelles responsible for making proteins, inflating its volume. The extra ribosomes are then degraded and discarded during the sleep part of the cycle.

The liver is a particularly time-sensitive organ, synchronised with the body’s primary circadian clock, a group of 20,000 nerve cells called the suprachiasmatic nucleus and located in the hypothalamus.

The 350 genes that govern the liver’s roles in metabolism and detoxification all express according to a 24-hour cycle, being “reset” by daylight.

“Many of them are also influenced by the rhythm of food intake and physical activity, and we wanted to understand how the liver adapts to these fluctuations,” says Schibler.

He and colleagues reported that the resetting did not occur in mice when their circadian rhythm was inverted, even though they consumed the same amount of food.

Quite what the implications are of constraining the regular swelling remain unclear, as is the question of whether findings in a mouse model are directly applicable to humans.

A study in 1985 established that human livers also enlarge and shrink during each 24-hour period. The degree to which the finding is analogous to the Geneva mouse study is imprecise, however, because the earlier work was conducted in order to compare liver growth between healthy and alcoholic subjects.

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