MIT Reveals How High-Fat Diets Quietly Prime the Liver for Cancer

janrinok writes:

https://scitechdaily.com/mit-reveals-how-high-fat-diets-quietly-prime-the-liver-for-cancer/

A fatty diet doesn't just damage the liver - it rewires its cells in ways that give cancer a dangerous head start.

Eating a diet high in fat is one of the strongest known risk factors for liver cancer. New research from MIT explains why, showing that fatty diets can fundamentally change how liver cells behave in ways that make cancer more likely to develop.

The study found that when the liver is exposed to a high-fat diet, mature liver cells called hepatocytes undergo a striking shift. Instead of maintaining their specialized roles, these cells revert to a more primitive, stem-cell-like state. While this transformation helps the cells cope with the ongoing stress caused by excess fat, it also leaves them far more vulnerable to becoming cancerous over time.

"If cells are forced to deal with a stressor, such as a high-fat diet, over and over again, they will do things that will help them survive, but at the risk of increased susceptibility to tumorigenesis," says Alex K. Shalek, director of the Institute for Medical Engineering and Sciences (IMES), the J. W. Kieckhefer Professor in IMES and the Department of Chemistry, and a member of the Koch Institute for Integrative Cancer Research at MIT, the Ragon Institute of MGH, MIT, and Harvard, and the Broad Institute of MIT and Harvard.

The team also pinpointed several transcription factors that appear to drive this cellular regression. Because these molecules help control whether liver cells stay mature or revert to an immature state, they may offer promising targets for future drugs aimed at reducing cancer risk in vulnerable patients.

High-fat diets are known to promote inflammation and fat buildup in the liver, leading to a condition called steatotic liver disease. This disorder can also result from other long-term metabolic stresses, including heavy alcohol use, and may progress to cirrhosis, liver failure, and eventually cancer.

To better understand what drives this progression, the researchers focused on how liver cells respond at the genetic level when exposed to a high-fat diet, especially which genes are activated or shut down as damage accumulates over time.

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