The Liver's Internal Clock Times When It Releases Metabolism Signals, Study Finds

The liver releases proteins that help coordinate metabolism throughout the body on a precise daily schedule, driven by its own internal molecular clock, according to a study by researchers at UT Health San Antonio, the academic health center of the University of Texas at San Antonio. The study, published in the journal Nature Communications, found that many of these metabolism-regulating proteins follow a set daily release pattern.

"Any cell with a nucleus is likely to express the molecular clock. We are interested in how cells work together and coordinate their activities," said Kevin Koronowski, assistant professor in the Department of Biochemistry and Structural Biology at UT Health San Antonio's Long School of Medicine. Nearly every cell in the body carries its own molecular clock, but researchers are still working out how these individual clocks coordinate with one another.

Because irregular eating patterns and disrupted sleep have long been associated with higher risk of obesity, diabetes and other metabolic disorders, and because the liver is central to metabolism, the researchers investigated how its internal clock controls the release of proteins that signal to other organs, such as fat tissue. "We thought the time-dependent release of proteins may be important for coordinating metabolism in tissues like fat or muscle," said Christopher Litwin, a PhD student in Koronowski's lab and the study's first author.

A key finding involved endostatin, a protein released by the liver: it was most effective at promoting fat breakdown when its release followed the liver's natural daily rhythm, suggesting that endostatin-based treatments could work differently depending on the time of day they are given. "We want to find the next GLP-1 drug, or even something better that is waiting to be discovered," Koronowski said, adding that the team is continuing to investigate potential therapeutic applications of this timing.