UNITS Uncovers Clue for Developing Non-Alcoholic Fatty Liver Disease Treatment

A new factor regulating the onset of non-alcoholic fatty liver disease caused by obesity has been discovered.

Professor Janghyun Choi's team from the Department of Life Sciences at UNIST and Professor Seongho Park's team found that the thyroid hormone receptor-associated protein Thrap3 increases in patients with non-alcoholic fatty liver disease and in animals (mice).

They confirmed that this protein worsens non-alcoholic fatty liver disease by inhibiting the activity of adenosine monophosphate-activated protein kinase (AMPK), a key regulator of lipid metabolism in the liver.

Non-alcoholic fatty liver disease is a metabolic disorder encompassing a broad range of conditions such as steatohepatitis and cirrhosis caused by inflammation due to excessive fat accumulation. Since no clear treatment has been developed to date, various studies are being conducted for its treatment.

The research team confirmed through animal experiments that Thrap3 protein directly binds to AMPK in the liver.

This interferes with the movement of AMPK from the nucleus to the cytoplasm. It also inhibits the effect of autophagy, which breaks down neutral fats and lowers cholesterol levels. In other words, suppressing the expression of Thrap3 can effectively treat non-alcoholic fatty liver disease.

A research diagram demonstrating the mechanism of non-alcoholic fatty liver disease development and improvement effects according to the regulation of adenosine monophosphate-activated protein kinase activity and autophagy by phosphorylation through Thrap3.

Professor Janghyun Choi from the Department of Life Sciences explained, “We have been building treatment strategies for non-alcoholic fatty liver disease but faced many limitations. With the discovery of the Thrap3 gene, we have newly proposed an effective treatment method for non-alcoholic fatty liver disease.”

Additionally, the research team confirmed that inhibiting Thrap3 effectively improves the stage of non-alcoholic steatohepatitis, an inflammatory disease caused by fatty liver.

This study was conducted with support from the Ministry of Science and ICT, the National Research Foundation of Korea, the Korea Mouse Phenotyping Consortium (KMPC), and the UNIST Future-Leading Project.

The research results were published online on August 1 in the prestigious life sciences journal Experimental and Molecular Medicine.

Professor Janghyun Choi and Professor Seongho Park served as corresponding authors of this paper, with Dr. Hyunjun Jang and Dr. Yohan Lee from UNIST participating as co-first authors.

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