High-Fat Diets Linked to Faster Liver Cancer Growth
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High-Fat Diets & Liver Cancer: New Research Reveals Cellular shift
A diet high in fat is one of the strongest contributors to liver cancer risk. New research from MIT sheds light on why this happens, showing that fatty diets can fundamentally alter liver cells in ways that make cancer more likely to develop.
The researchers discovered that when the liver is repeatedly exposed to a high-fat diet, mature liver cells called hepatocytes undergo a major change.Instead of remaining fully specialized, these cells shift into a more primitive, stem-cell-like state. this change allows them to better withstand the stress caused by excess fat, but over time it also increases their vulnerability to becoming cancerous.
“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 identified several transcription factors that appear to regulate this cellular shift. These factors may eventually serve as targets for drugs designed to reduce the risk of tumor formation in people who are especially vulnerable.
Shalek; Ömer Yilmaz, an MIT associate professor of biology and a member of the Koch Institute; and Wolfram Goessling, co-director of the Harvard-MIT Program in Health Sciences and Technology, are the senior authors of the study, which was published on December 22 in Cell. MIT graduate student Constantine Tzouanas, former MIT postdoc Jessica Shay, and Massachusetts General Brigham postdoc Marc Sherman are the co-first authors of the paper.
How Fatty Diets Trigger Liver Cell Reversion
High-fat diets can cause inflammation and fat accumulation in the liver, leading to a condition known as steatotic liver disease. This disease may also arise from long-term metabolic stressors such as heavy alcohol consumption and can progress to cirrhosis, liver failure, and ultimately cancer.
In this study, the researchers set out to understand how liver cells respond at a molecular level when exposed to a high-fat diet, focusing on which genes become more or less active as the stress continues.
To investigate this process, the team fed mice a high-fat diet and used single-cell RNA-sequencing to analyse liver cells at key stages of disease progress. This approach allowed them to follow changes in gene activity as the animals progressed from liver inflammation to tissue scarring and