Liver Protein Acts as Daily Fat-Secretion Timekeeper, Study Finds
A new study has identified a key protein that regulates the liver's daily rhythm of fat secretion, a process crucial for metabolic health. Disruption of this rhythm is linked to serious diseases.
A study published in Nature Communications on March 19, 2026, by Salk Institute researchers identified the protein Fibroblast Growth Factor 1 (FGF1) as a regulator of the daily rhythm of fat secretion from the liver.
The Circadian Rhythm of Liver Fat
The liver secretes fat into the bloodstream on a daily schedule to provide energy to peripheral tissues. This process follows a circadian rhythm, the body's internal 24-hour clock. When this rhythm is disrupted, it is associated with metabolic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD).
"We knew that liver fat metabolism follows a circadian rhythm, but the molecular logic connecting the clock to that output was unclear. FGF1 turned out to be a key timekeeper—a signal the liver uses to coordinate when and how much fat it secretes," stated Ronald Evans, a senior author of the study.
Key Findings on FGF1
The research found that FGF1 production in the liver itself follows a circadian pattern, directly influencing the timing of fat release.
- Mechanism: FGF1 acts as an output of the liver's internal circadian clock. It binds to a receptor on liver cells, initiating a signaling cascade. This cascade involves a protein typically associated with cellular stress response, which ultimately instructs the liver to package and release fat.
- Consequences of Disruption: In mouse models, the absence of liver-specific FGF1 disrupted this daily rhythm. This led to fat accumulation in the liver and accelerated progression of MASLD.
- Therapeutic Potential: Restoring FGF1 in models with established MASLD stalled disease progression.
The activation of a known cellular stress sensor as part of a normal daily process was an "unexpected" finding, noted co-first author Benan Pelin Sermikli.
Reframing a Protein's Role and Disease Context
According to the researchers, this finding reframes the understanding of that stress-sensor protein's role in normal metabolic health.
Co-corresponding author Michael Downes described the research as building on "an emerging picture of FGF1 as a systemic lipid trafficker." MASLD is a common chronic liver condition that can progress to more severe liver disease, cancer, cardiovascular disease, and diabetes.
The study was funded by the National Institutes of Health and the Larry L. Hillblom Foundation. Other authors included researchers from the Salk Institute and the University of Groningen.