Laboratory mice usually have unlimited access to food at all times. However, in these experiments, Sarkar withheld the animals from his food for 24 hours, then fed them ad libitum for 24 hours before he fasted for 24 hours. She then analyzed cell division in the livers of the animals after they had been fed an intermittent fasting diet for 1 week and 3 weeks, and compared them to normal-fed animals.
“Shortly after refeeding began, we found that cell turnover in the liver increased quite dramatically,” said Nusse. There were cells. This was very exciting.”
The liver’s role in metabolism means that the ratio of liver weight to body weight must remain constant in order for the organ to function efficiently. This is why the liver regenerates to a normal size even if part of the liver is removed.
Sarkar found that the cell division she observed was caused by a decrease in the liver-to-body weight ratio of study animals after a week of intermittent fasting. She also found that most of the cell divisions were localized to hepatocytes near the central veins of the organ.
Further investigation identified two molecular pathways involved in maintaining appropriate liver size in fasted animals. One is a growth factor called fibroblast growth factor (FGF), which is produced in the gut and travels throughout the body. The other is a family of proteins called Wnts, which are essential for embryonic development and the growth and maintenance of many tissues. Wnt proteins are secreted by central venous endothelial cells, but unlike FGF, they travel only short distances. The two signals overlap in hepatocytes near the central vein (called pericentral hepatocytes) to stimulate cell division after fasting.
“Interestingly, the Wnt pathway is not affected by intermittent fasting,” said Nusse, who identified the first Wnt protein in 1982. Intermittent fasting and other changes in food supply stimulate the production of circulating FGFs in the liver. It awakens hepatocytes from dormancy, and Wnt proteins then signal cells near the central vein to divide. ”
Sarkar next tested the effects of intermittent fasting in mice genetically engineered to be unable to respond to either FGF or Wnt signals. At that stage of the study, “the effects of intermittent fasting were attenuated,” Nusse said. “The cells more or less lost their ability to divide, which very strongly indicates that both of these signaling pathways are required to see the effects of fasting on cell replication.”
Researchers don’t know if fasting’s increased cell proliferation in the liver has any health benefits. It’s a study. They now plan to expand the study to include other types of diets, including ketogenic and high-fat diets.
“I wouldn’t recommend starting intermittent fasting to improve liver health,” Nusse said. , shows that it should be understood with a grain of salt.”
Researchers at the Chan-Zuckerberg Biohub also contributed to this work.
This research was supported by the Steinhardt-Reed Foundation, Howard Hughes Medical Institute, Department of Defense, and the Damon Runyon Foundation for Cancer Research.
