Prolonged consumption of high-fat diets can push liver cells into a stress-survival mode that significantly increases the risk of cancer, according to a new study by researchers at the Massachusetts Institute of Technology.
The research shows that repeated exposure to fatty foods causes mature liver cells, known as hepatocytes, to lose their specialised functions and revert to a more primitive, stem-cell-like state. While this shift helps the cells survive metabolic stress, it also leaves the liver less capable of performing its normal functions and more vulnerable to tumour formation, offering a biological explanation for why fatty liver disease often precedes liver cancer.
Using single-cell RNA sequencing, the researchers tracked gene activity in mice fed a high-fat diet as their liver disease progressed from inflammation to scarring and eventually cancer. They found that genes promoting cell survival and growth were activated early, while those responsible for metabolism and protein secretion were gradually switched off. By the end of the study, nearly all mice on the high-fat diet developed liver cancer.
The team identified several transcription factors that regulate this cellular shift, some of which are already being targeted by drugs under development or in clinical trials for severe forms of fatty liver disease. Analysis of human liver samples showed similar genetic patterns, with patients displaying higher levels of survival-related genes and lower levels of normal liver function genes experiencing poorer outcomes once cancer developed.
The researchers estimate that while the process unfolds over about a year in mice, it may take decades in humans, depending on diet and other risk factors such as alcohol use and viral infections. Future studies will examine whether dietary changes or weight-loss treatments can reverse these cellular changes and reduce cancer risk.
ANI
