The human liver. Credit: Department of Histology, Jagiellonian University Medical College
Key points:
- A study in mice shows intermittent fasting spurs liver cells to divide rapidly.
- The liver may be more affected by diet than previously thought.
- The team is now expanding their research to analyze the effects of other types of diets, such as ketogenic and high-fat.
In research that challenges long-standing beliefs, scientists at Stanford Medicine have found that intermittent fasting spurs liver cells, in laboratory mice, to divide rapidly. Previously, it was thought that cells in the adult liver rarely divide, and when they do, it is primarily to repair damage to the organ. The study is also the first to show an immediate effect of diet on liver cell biology.
For the study, published in eLife, researchers withheld food from mice for 24 hours, then allowed them to feed freely for 24 hours before another fast of 24 hours. The team then analyzed cell division in the animals’ livers after one week and three weeks of the intermittent fasting diet and compared it with that of mice who had been fed normally.
“We saw that the turnover of cells in the liver went up fairly dramatically shortly after refeeding began,” said Roeland Nusse, professor of developmental biology. “There were many more new cells than in animals that had been fed on a standard diet.”
The researchers found that the cell division observed was sparked by a decrease in the ratio of liver to body weight in the study animals after a week of intermittent fasting. Most of the cell division was localized to liver cells near the central vein of the organ.
Further investigation identified two molecular pathways responsible for maintaining appropriate liver size in the fasted animals. One is a growth factor called fibroblast growth factor, or FGF, that is produced by the intestines and travels throughout the body. The second, a family of proteins called Wnts, is crucial to embryonic development and the growth and maintenance of many tissues.
“Interestingly, the Wnt pathway is not affected by intermittent fasting, but the production of FGF is,” said Nusse, who identified the first Wnt protein in 1982. “Intermittent fasting or other changes in the food supply stimulate the production of FGF, which circulates to the liver. It weakens the liver cells from resting, then Wnt proteins give those near the central vein the signal to divide.”
When researchers tested mice that had been genetically engineered to be unable to respond to either the FGF signal or the Wnt signal, the effect of intermittent fasting was attenuated.
At this point in the research, the team don’t know whether the increased cell proliferation in the liver due to fasting has human health benefits. They are now planning to extend their studies to include other types of diets, including ketogenic or high-fat.
“I wouldn’t recommend that people start intermittently fasting to improve their liver health,” Nusse said. “But it’s an exciting observation—it shows that the idea that the liver is a tissue that turns over slowly should be taken with a grain of salt.”
Information provided by Stanford Medicine.