A new study from MIT shows how eating a high-fat diet can change the liver in dangerous ways, eventually increasing the risk of liver cancer.
The research helps explain why people who eat a lot of fatty foods are more likely to develop this serious disease.
The study, published in the journal Cell, shows that a high-fat diet causes liver cells, called hepatocytes, to go through a major transformation. Normally, these cells are mature and help the liver perform important jobs like breaking down food and removing toxins. But when exposed to too much fat over time, the cells start to act more like immature stem cells.
This shift allows them to survive the damage caused by fatty foods. However, being in this immature state also makes them more likely to become cancerous if something goes wrong later, such as a gene mutation. It’s like the cells are trying to protect themselves, but in doing so, they also become more dangerous in the long run.
The researchers fed mice a high-fat diet and watched how their liver cells changed over time. They used a tool called single-cell RNA sequencing to see which genes were turned on and off.
At first, the liver cells began turning on genes that help them survive and multiply. At the same time, they started turning off genes needed for normal liver functions, such as making enzymes and proteins.
These changes happened gradually, and eventually, most of the mice developed liver cancer. The researchers believe this is because the cells had already started to act like cancer cells—growing quickly and no longer behaving like normal liver cells. All it took was one more step, like a mutation, to trigger full-blown cancer.
One of the most interesting parts of the study was that the severity of damage did not matter as much as the fact that the cells had changed. The researchers also identified specific genes and molecules that control this transformation.
One of them, called SOX4, is usually only active during early development, not in the adult liver. Its presence in these liver cells suggests something has gone very wrong.
The team also looked at human liver samples from people with liver disease and found the same pattern. People with lower levels of normal liver function genes and higher levels of survival genes were more likely to die sooner after developing liver cancer. This confirms that what happened in mice is also happening in humans.
The good news is that the researchers now have some ideas for new treatments. Some of the genes they discovered are already being targeted by drugs for other liver diseases. One drug, already approved, targets a gene involved in these changes. Another drug is in clinical trials.
The researchers now want to find out if the damage caused by a high-fat diet can be reversed. Could switching back to a healthy diet or using weight-loss medications like GLP-1 drugs help restore the liver to its normal state? They also hope to develop new drugs that stop liver cells from changing into immature, cancer-prone cells in the first place.
This study shows how deeply a fatty diet can affect our organs. It doesn’t just make us gain weight—it can change how our cells behave at a genetic level. These changes might not cause cancer right away, but over many years, they can increase the risk in serious ways.
If you care about liver health, please read studies about Healthy liver, happy life: new advice for keeping your liver in top shape and findings of Ibuprofen may have significant impact on the liver.
If you care about liver health, please read studies about Fatty liver disease linked to severe infections and findings of A new drug for weight loss and liver health.
Copyright © 2025 Knowridge Science Report. All rights reserved.
