New research could open door to new liver treatments

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Monash University has announced that a team including its researchers has discovered that fructose causes liver toxicity by changing the barrier function of the intestine

It said the new discovery deepens understanding of how fructose affects the liver and could also protect it from numerous life-threatening diseases.

The new study, published today in Nature Metabolism, shows that fructose affects the liver only after it causes intestinal barrier disruption, therefore treatments that prevent barrier disruption could protect the liver from fructose-induced diseases including non-alcoholic fatty liver disease (NAFLD), fibrosis and cancer. 

Fructose is a simple sugar that can be found in high quantities in soft drinks, sauces and fast foods. Research has found that fructose is up to three times more potent than glucose in increasing liver fat.

Excessive fructose consumption has been linked to the recent surge in NAFLD - one of the most common metabolic disorders - and its associated co-morbidities, which include liver failure, cirrhosis, and cancer.

Professor Mark Febbraio from Monash’s Institute of Pharmaceutical Sciences was part of the international team of researchers led by Professor Michael Karin from The University of California San Diego.

Professor Febbraio said, “The findings from this study make it clear that fructose does its damage in the intestine and if intestinal barrier deterioration is prevented, the fructose does little harm to the liver.”

The international team of researchers found that by adding a cell signalling protein called ‘tumor necrosis factor’ (TNF) to hepatocytes stimulates the metabolism of fructose and increases the production of the enzymes that convert the molecule ‘acetyl CoA’ to fatty acids.

“A large increase in the expression of these enzymes was also detected in livers of fructose-fed mice,” said Professor Febbraio.

“Conversely, genetic modification that reduced TNF production was found to protect mice from fructose-provoked NAFLD, which is a very exciting step forward for the treatment of diseases which can evolve from this all too common liver disorder."

Monash said the study demonstrates that maintaining gut barrier integrity is a therapeutic target to treat liver disease associated with high fructose consumption. 

It said the researchers will now focus on screening drug candidates that target key proteins in the maintenance of gut barrier integrity.