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

Zika virus stifles pregnant women's weakened immune system to harm baby, study finds

August 21, 2017
The Zika virus, linked to congenital birth defects and miscarriages, suppresses a pregnant woman's immune system, enabling the virus to spread and increasing the chances an unborn baby will be harmed, a Keck School of Medicine ...

Novel approach to track HIV infection

August 18, 2017
Northwestern Medicine scientists have developed a novel method of tracking HIV infection, allowing the behavior of individual virions—infectious particles—to be connected to infectivity.

Faulty gene linked to obesity in adults

August 18, 2017
Groundbreaking new research linking obesity and metabolic dysfunction to a problem in the energy generators in cells has been published by researchers from the Harry Perkins Institute of Medical Research and The University ...

Two lung diseases killed 3.6 million in 2015: study

August 17, 2017
The two most common chronic lung diseases claimed 3.6 million lives worldwide in 2015, according to a tally published Thursday in The Lancet Respiratory Medicine.

New test differentiates between Lyme disease, similar illness

August 16, 2017
Lyme disease is the most commonly reported vector-borne illness in the United States. But it can be confused with similar conditions, including Southern Tick-Associated Rash Illness. A team of researchers led by Colorado ...

Addressing superbug resistance with phage therapy

August 16, 2017
International research involving a Monash biologist shows that bacteriophage therapy – a process whereby bacterial viruses attack and destroy specific strains of bacteria - can be used successfully to treat systemic, multidrug ...

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.