High-fat diets linked to liver cancer

Normal, non-cancerous liver tissue can act like tumour tissue when exposed to a diet high in fat, linking diet and obesity to the development of liver cancer.

That’s according to a new international study, published in the journal Cancer Research and led by Professor Sarah-Maria Fendt and her team at the VIB-KU Leuven Center for Cancer Biology.

Understanding how excess fat availability can drive liver cancer development is important to understand how the disease starts and how it can be treated. To explore this, researchers tested the metabolic changes in liver tissue from mice fed a high-fat diet at an early time point when no tumours were present, and late time point when tumours had formed.

They found that before there were any clues that cancer was developing, the liver tissue used glucose the same way that tumours would. This high use of glucose is one of the well-known hallmarks of cancer and is known as the Warburg effect.

After finding these early changes to liver tissue, the team investigated what happens when tumours have fully formed. One way they measured this was to test sensitivity to glucose, which is usually cleared away quickly by the body but is impaired in obesity-induced diabetic animals.

“Strikingly, mice fed a high-fat diet who had a large tumour burden could remove glucose from their blood as easily as healthy mice, despite being diabetic,” Prof Fendt said. “Using state-of-the-art 13C6-glucose tracing technology, we could observe how glucose molecules are used in cells and tissues, and we found that tumour tissue breaks down glucose in a consistent way, regardless of whether the mice were fed high-fat or normal diets.”

These findings suggest that when cancer cells develop from normal liver cells, their metabolism consistently increases glucose use. Since a high-fat diet causes these changes before cancer is present, this may mean that — in a high-fat diet — non-cancer liver tissue could be more likely to become cancerous.

The team also looked into deeper mechanisms for this effect. Co-lead author Dr Lindsay Broadfield, also from the VIB-KU Leuven Center for Cancer Biology, said, “We discovered that, before any cancer development, liver tissue exposed to high fat seemed to use an alternative pathway for fat breakdown in a cellular compartment called the peroxisome. Using cancer liver cells, we then confirmed that peroxisome metabolism increased cellular stress and glucose uptake.”

Fat can be used by cells in several ways — for energy, to stimulate growth pathways, or to be stored for later use. The scientists used the Lipometrix lipidomics platform at KU Leuven to see if there was anything unique about the fate of fat in tumour cells and found that the fat species and content in tumour cells were indeed different from non-cancerous liver tissue close to the tumours.

The team concluded that their findings are important to better understand the metabolic links between diet, obesity and liver cancer development, and can provide new therapeutic avenues.

Image credit: ©stock.adobe.com/au/happy_lark

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