Of Mice and Metabolism

Many biological processes exhibit daytime differences governed by rhythmic exposure to sunlight, termed circadian rhythms. College research in mice found that a protein critical to intestinal barrier function—helping the gut absorb nutrients while blocking harmful pathogens—is rhythmically controlled by nighttime liver metabolism of the molecule tryptophan.

The study found that when the amino acid tryptophan is ingested, it travels to the liver. There, tryptophan produces metabolites—molecular byproducts of metabolism—that activate a protein called the aryl hydrocarbon receptor or Ah receptor, which then works to improve barrier function in the gut.

Gary Perdew, the H. Thomas and Dorothy Willits Hallowell Chair in Agricultural Sciences and lead author on the paper, said the findings provide clues on how diet can be used to improve intestinal barrier function.

“Ingesting tryptophan, which is plentiful in protein-rich foods, kick-starts this process that results in better barrier function in the gut, suggesting that protein is a really important part of your diet,” he said. He noted that even though this work was conducted in mice, the Ah receptor is also abundant in humans. “We also observed that this process increases during waking hours, indicating it might be even more important to have protein at breakfast.”

For the study, the researchers fed the mice on a schedule meant to mimic how humans usually eat. They withheld food from the mice during the day, when they are typically sleeping, and reintroduced food during the evening, when mice are more active. This approach mirrors how humans fast overnight and then eat breakfast in the morning.

The researchers analyzed the mice’s liver and serum every four hours, allowing them to observe the effects of tryptophan ingestion. They discovered that the period of an animal’s circadian rhythm during which active eating occurs leads to an increase in tryptophan metabolites produced in the liver and present in serum.

—Katie Bohn