The AEBP1 gene could play a key role in the development and severity of liver disease

Researchers have discovered that a gene known as AEBP1 could play a central role in the development, severity, and potential treatment of liver disease, according to a study by Temple University's Geisinger Obesity Institute and the Translational Genomics Research Institute (TGen), affiliate of the City of Hope.

The results are detailed in a study published in the scientific journal PLoS One.

The results of the study suggest that an increase in AEBP1 expression is correlated with the severity of liver fibrosis in patients with NASH (nonalcoholic steatohepatitis), which is a type of NAFLD (non-alcoholic fatty liver disease), the most common cause of liver damage. NASH indicates both inflammation and damage to liver cells, as well as fat in the liver.

Given the strong link between fibrosis and the risk of liver death, efforts to identify and characterize the specific mechanisms contributing to the progression of NAFLD are essential to the development of effective therapeutic and preventive strategies. "

Dr. Johanna DiStefano, Head of the Diabetes and Fibrous Diseases Unit, TGen

One of the main conclusions of the study is that AEBP1 regulates the expression of a network of at least nine genes related to fibrosis: AKR1B10, CCDC80, DPT , EFEMP1, ITGBL1, LAMC3, MOXD1, SPP1 and STMN2.

"These results indicate that AEBP1 could be a central regulator of a complex gene expression network for fibrosis in the human liver," said Dr. DiStefano, lead author of the study.

The study suggests that:

• AEBP1 contributes to liver fibrosis by modulating a gene network specific for stellate cells, the key fibrogenic cells of the liver.
• The expression of AEBP1 is increased by factors related to obesity related to NAFLD, including glucose, fructose and palmitate sugars, a fatty acid that is commonly found in processed foods.
• Two microRNAs – miR-372-3p and miR-373-3p – which otherwise limit the expression of AEBP1, are reduced in NASH patients with advanced fibrosis. MicroRNAs are a newly discovered clbad of non-coding RNAs that play a key role in the regulation of gene expression.

"Our work shows that AEBP1 corresponds to the onset and severity of fibrosis in NASH patients and suggests that AEBP1 could represent a specific therapeutic target to prevent the development of NASH fibrosis," said Dr. Glenn S. Gerhard, director of the department of medicine. Genetics and Molecular Biochemistry at the Lewis Katz School of Medicine at Temple University. Dr. Gerhard is the principal author of the study.

The National Institutes of Health (NIH) funded this study. The expression of AEBP1 increases with the severity of fibrosis in NASH and is regulated by glucose, palmitate and miR-372-3p.