Khaberni - A new study warns that high-fat diets not only harm the liver but also reprogram their cells to become more susceptible to becoming cancerous.
The study, published in the journal "Cell" and conducted by researchers from the Massachusetts Institute of Technology (MIT) in the USA, showed that mature liver cells, known as hepatocytes, respond to the stress of consuming high amounts of fats by reverting to a primitive state akin to stem cells. This step helps them survive in a stressful environment, but also opens the door for the onset of cancer over the long term.
Alex Shalek, a senior researcher in the study and director of MIT's Institute for Medical Engineering and Science, said that cells "when exposed to repeated stress, such as a high-fat diet, make decisions that help them survive but at a costly price of increased susceptibility to cancerous transformation."
From survival to cancer
The researchers explained that high-fat diets lead to fat accumulation and inflammation of the liver, a condition known as fatty liver disease, which may later progress to fibrosis and liver failure, then cancer.
During the study, the team fed mice a high-fat diet and then used advanced techniques to analyze gene activity within liver cells at individual cellular stages of disease development.
They found that liver cells activate genes that help them resist cell death and proliferate, while at the same time they shut down essential genes for normal liver functions, such as producing enzymes and vital substances necessary for body functioning.
The researcher Konstantinos Tsouanas, co-author of the study, described this change as a "dangerous trade-off, where the cell chooses individual survival at the expense of the entire tissue's health."
The team noted that cells returning to an immature state become more prone to cancerous transformation if they later undergo genetic mutations.
Tsouanas explained that these cells "have already activated genes needed to become cancerous and discarded their mature identity that was restraining their proliferation, giving them an 'early start' towards cancer once any genetic malfunction occurs," and by the end of the experiment, most mice that consumed a high-fat diet had developed liver cancer.
New pharmaceutical targets
The study uncovered a range of genetic transcription factors controlling this cellular transformation, opening the door for developing new drugs to prevent cancer in at-risk patients.
It is notable that one of these molecular targets is the thyroid hormone receptor, already targeted by a newly approved drug for treating a form of advanced fatty liver disease. Other drugs are currently being tested in clinical trials based on similar results.
The study also highlighted another genetic factor called "SOX4," typically active during embryonic development and non-active in a normal liver, but reactivated under the influence of a high-fat diet.
Results applicable to humans
To ensure the relevance of the findings to humans, the researchers analyzed liver samples from patients at different stages of the disease, and the same genetic pattern appeared in humans, showing a decline in normal liver functions against rising indicators of immature cells.
More importantly, the team was able to predict patient survival rates based on these genetic changes, where increased genes for cellular survival and decreased genes for normal functioning correlated with worse outcomes.
Can the course be reversed?
The researchers believe that disease progression in humans can take many years, possibly up to 20 years, and is influenced by other factors such as alcohol or viral infections.
The team is currently studying whether it is possible to reverse these changes through a return to a healthy diet, or by using weight loss drugs like GLP-1 agonists, alongside testing the possibility of targeting discovered genetic factors to prevent the transformation of liver disease into cancer.
In conclusion, Shalek said: "We now have a deeper understanding of molecular mechanisms and new therapeutic targets that could truly make a difference in improving patients' future chances."
