New animal model may lead to treatments for common liver disease

July 3, 2012

Scientists at Texas Biomed have developed the laboratory opossum as a new animal model to study the most common liver disease in the nation – afflicting up to 15 million Americans – and for which there is no cure.

The condition, nonalcoholic steatohepatitis (NASH), resembles alcoholic , but occurs in people who drink little or no alcohol. The major feature of NASH is accumulation of fat in the , along with inflammation and functional damage. Most people with NASH feel well and are not aware that they have a liver problem. Nevertheless, NASH can progress to cirrhosis, in which the liver is permanently damaged and no longer able to work properly. NASH-related cirrhosis is the fourth most common indication for liver transplantation in the U.S.

NASH affects 2 to 5 percent of Americans – roughly six million to 15 million people. An additional 15 to 30 percent of Americans have excess fat in their livers, but no inflammation or liver damage, a condition called "fatty liver" or the non-progressive form of nonalcoholic fatty liver disease (NAFLD).

The study, published in the July issue of the American Journal of Physiology-Gastrointestinal and Liver Physiology, was supported by the National Institutes of Health and the Robert J. Kleberg, Jr., and Helen C. Kleberg Foundation.

"This is the type of model in which to develop mechanism-based therapies," writes Geoffrey C Farrell, M.D., of the Australian National University Medical School in Canberra, in a journal editorial.

Both NASH and NAFLD are becoming more common, possibly because of the greater number of Americans with obesity and its important health complications, type 2 diabetes, high blood cholesterol levels, high blood pressure and other risk factors for heart attack and stroke. In the past 10 years, the prevalence of obesity has doubled in adults and tripled in children. It was previously reported by other scientists that the prevalence of NAFLD and NASH in a cohort of middle-aged patients in San Antonio is 46 percent and 12 percent, respectively.

"It now seems likely that genetic factors, such as those important for diabetes and high cholesterol levels, are what determines why a small proportion of those with fatty liver develop NASH and its complications of cirrhosis and liver cancer," said Farrell.

In the new study, high responding opossums developed elevated cholesterol and fatty liver disease when fed a high cholesterol and high fat diet, whereas low responding opossums did not. High responders carry a mutated ABCB4 gene, which affects their ability to secrete excess cholesterol from the liver into bile which, in turn, transports the cholesterol to the intestines for excretion from the body. As a consequence, opossums with the mutated gene accumulate cholesterol in the liver and ultimately in the blood.

"We showed that the fatty livers of high responders contain a tremendous amount of cholesterol," said first author Jeannie Chan, Ph.D., of Texas Biomed. "The is a new for investigating the mechanism by which cholesterol mediates liver injury, which will lead to a better understanding of the role of dietary in the development of NASH."

Explore further: Researchers identify changes in cholesterol metabolic pathways

Related Stories

Researchers identify changes in cholesterol metabolic pathways

June 7, 2012
A new study from the Virginia Commonwealth University School of Medicine has identified molecular changes responsible for abnormal cholesterol production and metabolism in the livers of patients with a common liver condition, ...

Coffee consumption reduces fibrosis risk in those with fatty liver disease

February 2, 2012
Caffeine consumption has long been associated with decreased risk of liver disease and reduced fibrosis in patients with chronic liver disease. Now, newly published research confirms that coffee caffeine consumption reduces ...

Obesity and diabetes epidemics spur increase in nonalcoholic steatohepatitis

December 14, 2011
Nonalcoholic steatohepatitis (NASH) occurs when fat builds up in the liver. This accumulation of fat damages the liver and leads to cirrhosis. NASH is rapidly increasing in the U.S. mainly related to the epidemics of obesity ...

Modest alcohol consumption lowers risk and severity of liver disease

April 19, 2012
People with nonalcoholic fatty liver disease (NALFD) who consume alcohol in modest amounts – no more than one or two servings per day – are half as likely to develop hepatitis as non-drinkers with the same condition, ...

Recommended for you

Anti-malaria drug shows promise as Zika virus treatment

November 17, 2017
A new collaborative study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) and UC San Diego School of Medicine has found that a medication used to prevent and treat malaria may also be effective ...

Decrease in sunshine, increase in Rickets

November 17, 2017
A University of Toronto student and professor have teamed up to discover that Britain's increasing cloudiness during the summer could be an important reason for the mysterious increase in Rickets among British children over ...

Scientists identify biomarkers that indicate likelihood of survival in infected patients

November 17, 2017
Scientists have identified a set of biomarkers that indicate which patients infected with the Ebola virus are most at risk of dying from the disease.

Research team unlocks secrets of Ebola

November 16, 2017
In a comprehensive and complex molecular study of blood samples from Ebola patients in Sierra Leone, published today (Nov. 16, 2017) in Cell Host and Microbe, a scientific team led by the University of Wisconsin-Madison has ...

Study raises possibility of naturally acquired immunity against Zika virus

November 16, 2017
Birth defects in babies born infected with Zika virus remain a major health concern. Now, scientists suggest the possibility that some women in high-risk Zika regions may already be protected and not know it.

A structural clue to attacking malaria's 'Achilles heel'

November 16, 2017
Researchers from The Scripps Research Institute (TSRI) and PATH's Malaria Vaccine Initiative (MVI) have shed light on how the human immune system recognizes the malaria parasite though investigation of antibodies generated ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.