UCSD researchers are looking into how high-fat diets could lead to liver failure and cancer. Photo credit: abcnews.go.com

Attacking a protein that causes inflammation could be the key to treating a form of disease that could lead to liver failure and is increasingly prevalent as Americans grow heavier, according to researchers at UC San Diego.

Interfering with the protein’s synthesis by using genetic tools or medication, such as the anti-psoriasis and rheumatoid arthritis drug, Enbrel, the researchers inhibited both the development of the harmful protein and its progression to cancer.

“Given the dramatic and persistent increase in the incidence of obesity and its consequences in the United States and elsewhere, these studies have a high impact on a major public health problem,” said Michael Karin, a UCSD professor of pharmacology.

The scientists found that the development of what they call NASH – non-alcoholic steatohepatitis – can lead to cirrhosis and liver cancer, but it can be inhibited by influencing the particular inflammatory protein.

NASH, which doctors are seeing more often because of increasing obesity, has become the number one cause of liver failure and transplantation.

“These findings strongly call for clinical testing of relevant drugs in human NASH and its complications,” said Karin of the UCSD Laboratory of Gene Regulation and Signal Transduction. “Our research has shown that, at least in this mouse model, chemical compounds that include already clinically approved drugs that inhibit protein aggregation can also be used to prevent NASH caused by a high fat diet.”

NASH is characterized by inflammation and fibrosis, which damage the liver and can lead to cirrhosis, hepatocellular carcinoma – the major form of liver cancer – and loss of function. Often, the only remedy is organ transplantation, according to UCSD.

The researchers conducted their study in mice. It’s been difficult to perform such experiments in the past because of a limited quantity of mouse models, the scientists said.

Using the new model, the researchers showed that a protein called tumor necrosis factor, which is involved in the body’s inflammatory response, plays a critical role in both NASH development and progression to fibrosis and cancer.

The results of the study, in which Karin was assisted by researchers at the Sanford-Burnham Medical Research Institute, along with others from Japan and Spain, were published online in the journal Cancer Cell.

Their research was funded by grants from, among others, the National Institutes of Health, The Rotary Foundation, the California Institute for Regenerative Medicine and the American Liver Foundation.

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