Fatty liver: Turning off TAZ reverses disease

October 27, 2016, Columbia University Medical Center
Mice were fed a diet rich in fat and sugar until they developed NASH-like features in their livers. On the left, staining reveals the most important feature of NASH -- fibrosis -- as dark linear structures (indicated with arrows). On the right, fibrosis reverted when TAZ was silenced in the mice with NASH. Credit: Source: Dr. Wang in the Tabas lab, Columbia University Medical Center

Scientists at Columbia University Medical Center (CUMC) have identified a factor in liver cells that is responsible for turning a relatively benign liver condition, present in 30 percent of U.S. adults, into a serious disease that can lead to liver failure.

The study was published online today in Cell Metabolism.

With the rise of obesity in the U.S., the incidence of nonalcoholic fatty disease (NAFLD)—in which excess fat fills the liver—has risen to epidemic levels. The extra liver fat is generally benign, but in one in five people, NAFLD evolves into a more serious condition, nonalcoholic steatohepatitis (NASH).

In NASH, the liver becomes inflamed and criss-crossed by fibrous scar tissue, and liver cells start dying. Patients with NASH are at risk of and , but there are no drugs on the market that can slow or stop the disease.

Because the amount of fibrosis in the liver is associated with a greater risk of death from NASH, Xiaobo Wang, PhD, associate research scientist in the Department of Medicine at CUMC, looked for ways to stop fibrosis in a mouse model of NASH.

He found that in liver cells, TAZ, a previously unknown factor in NASH, plays a critical role in initiating fibrosis, and that fibrosis stops in mice with NASH when TAZ is inactivated in . With TAZ shut down, existing fibers in the liver also dissolved, essentially reversing the disease. Two other critical features of NASH, inflammation and cell death, were also reduced when TAZ was turned off. Fat accumulation in the liver was unaffected.

Based on their examination of from NAFLD and NASH patients, Drs. Wang and Tabas believe that TAZ works in the same way in people.

"We think that by stopping fibrosis through TAZ and its partners, we may be able to prevent the serious consequences of NASH, including liver failure and liver cancer," said Ira Tabas, MD, PhD, Richard J. Stock Professor and vice-chair of research in the Department of Medicine and professor of pathology & cell biology (in physiology and cellular biophysics) at CUMC.

The study is titled, "TAZ/WWTR1 Promotes Hepatic Inflammation and Fibrosis in Nonalcoholic Steatohepatitis."

Explore further: Hormone identified that limits liver fibrosis

Related Stories

Hormone identified that limits liver fibrosis

October 13, 2016
Nonalcoholic steatohepatitis (NASH) has been emerging worldwide and effective treatment, especially for liver fibrosis, is essential for improving the prognosis. A Japanese research team has identified and clarified the mechanism ...

Simple blood test could vastly improve detection rates of severe liver disease

October 6, 2016
A new non-invasive method of predicting the risk of developing a severe form of liver disease could ensure patients receive early and potentially life-saving medical intervention before irreversible damage is done.

MRI technology quantifies liver response in nonalcoholic steatohepatitis patients

August 19, 2016
Researchers at the University of California San Diego School of Medicine have found that a form of magnetic resonance imaging (MRI) that non-invasively measures fat density in the liver corresponds with histological (microscopic ...

Technique may identify patients with fast-progressing fibrosis in nonalcoholic fatty liver disease

October 11, 2016
Combining multiple non-invasive measures, researchers at University of California San Diego School of Medicine describe a novel method to quantify the progression of nonalcoholic fatty liver disease (NAFLD) to its more dangerous ...

NASH associated with a 50 percent higher chance of death compared with NAFLD

April 24, 2015
Results from a large population-based cohort of almost a million people in the UK found that the chances of dying from non-alcoholic steatohepatitis (NASH), over a 14-year period, was approximately 50% higher than for those ...

Estrogen protects women with NASH from severe liver fibrosis

October 29, 2013
New research suggests that estrogen protects women with nonalcoholic steatohepatitis (NASH) from severe liver fibrosis. According to the study published online in Hepatology, a journal of the American Association for the ...

Recommended for you

PET scans to optimize tuberculosis meningitis treatments and personalize care, study finds

December 6, 2018
Although relatively rare in the United States, and accounting for fewer than 5 percent of tuberculosis cases worldwide, TB of the brain—or tuberculosis meningitis (TBM)—is often deadly, always hard to treat, and a particular ...

Silicosis is on the rise, but is there a therapeutic target?

December 6, 2018
Researchers from the CNRS, the University of Orléans, and the company Artimmune, in collaboration with Turkish clinicians from Atatürk University, have identified a key mechanism of lung inflammation induced by silica exposure, ...

Infectivity of different HIV-1 strains may depend on which cell receptors they target

December 6, 2018
Distinct HIV-1 strains may differ in the nature of the CCR5 molecules to which they bind, affecting which cells they can infect and their ability to enter cells, according to a study published December 6 in the open-access ...

Protecting cell powerhouse paves way to better treatment of acute kidney injury

December 6, 2018
For the first time, scientists have described the body's natural mechanism for temporarily protecting the powerhouses of kidney cells when injury or disease means they aren't getting enough blood or oxygen.

New study uncovers why Rift Valley fever is catastrophic to developing fetuses

December 5, 2018
Like Zika, infection with Rift Valley fever virus can go unnoticed during pregnancy, all the while doing irreparable—often lethal—harm to the fetus. The results of a new study, led by researchers at the University of ...

Study highlights potential role of bioaerosol sampling to address airborne biological threats

December 5, 2018
As a leading global city with a high population density, Singapore is vulnerable to the introduction of biological threats. Initiating an early emergency response to such threats calls for the rapid identification of the ...

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.