Our bodies run on an internal 24-hour clock that affects everything from sleep to metabolism. Now, scientists at Baylor College of Medicine have uncovered another piece of the puzzle: diet and genetics work together to set the rhythm of fat metabolism in the liver.
The study, published in Cell Metabolism, shows that genetic differences help determine when liver genes turn on and off during the day and how those patterns shift with diet.
“Our study provides new insights into the question, ‘Why do some people gain weight more easily or develop liver problems while others don’t, even when they eat similar diets?’” said corresponding author Dr. Dongyin Guan, assistant professor of medicine at Baylor and member of the Dan L Duncan Comprehensive Cancer Center.
Using human liver samples and mice with different genetic backgrounds, the researchers tracked how gene activity changes across the day. They found that thousands of genes showed rhythmic activity only in people with certain genetic variants. Diet added another layer: in mice fed a high-fat diet, some liver genes lost their rhythm, others gained one, and some stayed the same.
“Genes and diet work together to shape the liver’s daily rhythm, which in turn can affect how fats are processed and stored,” said co-first author Dr. Ying Chen, postdoctoral fellow in the Guan lab.
The team also discovered that genetics and diet together influence more than 80% of daily connections between DNA regions that regulate gene activity. One gene, ESRRγ, emerged as a key regulator. Mice lacking ESRRγ lost many of these rhythmic connections and showed disrupted fat metabolism.
The findings suggest that fat metabolism is both time-sensitive and gene-dependent. In mice, the size of fat droplets in the liver shifted across the day, but only when ESRRγ was active. The authors propose that the same principles may apply to other organs and diseases, supporting the possibility of personalized chronotherapy, tailoring mealtimes or scheduling treatments based on a person’s genetic profile to optimize health outcomes.
The study was supported by the American Liver Foundation, NIH, CPRIT Scholar Awards, V Foundation, USDA/ARS, Pew Foundation, Additional Ventures and the Fundamental Research Funds for the Central Universities of China-Xiamen University.