Emerging Therapeutic Strategy Against Non-Alcoholic Fatty Liver Disease Identified

Recent scientific investigations have pinpointed that the Thrap3 protein exacerbates NAFLD by impairing hepatic fat metabolism, indicating that interventions targeting Thrap3 may offer new therapeutic avenues for this condition.

Pioneering research, co-directed by Professor Jang Hyun Choi and Professor Sung Ho Park of the Biological Sciences Department at UNIST, has pinpointed a critical element in the progression of non-alcoholic fatty liver disease (NAFLD), frequently associated with obesity. This element, the Thrap3 protein, associated with thyroid hormone receptors, was found to amplify the severity of NAFLD by inhibiting the action of adenosine monophosphate-activated protein kinase (AMPK), an enzyme essential for managing fat metabolism in the liver.

Role and Impact of Thrap3 on NAFLD

NAFLD comprises a spectrum of metabolic disorders, including fatty hepatitis and cirrhosis, arising from excessive fat deposition in the liver. Until now, there have been scant effective treatments for NAFLD, making this new finding particularly notable for its therapeutic implications.

The study, a collaborative effort by professors Jang Hyun Choi and Sung Ho Park from UNIST, has identified a crucial component in the development of NAFLD, which obesity often precipitates. Image courtesy of UNIST.

Using rodent models, the investigative team illustrated that Thrap3 forms a direct bond with AMPK within the liver, obstructing AMPK’s migration from the nucleus to the cytoplasm and hindering autophagy. This process is vital for degrading triglycerides and reducing cholesterol. Therefore, suppressing Thrap3 could be a key strategy in effectively managing NAFLD.

Potential and Direction of the Research

“In the face of significant hurdles in devising treatments for non-alcoholic fatty liver disease, the identification of the Thrap3 gene stands as a potential breakthrough in our approach to this disease,” Professor Choi noted.

Graphic illustration of Thrap3’s role in NAFLD via the movement of AMPK. Courtesy of UNIST.

Furthermore, it has been confirmed that Thrap3 inhibition markedly enhances conditions related to non-alcoholic steatohepatitis, an inflammatory state derived from a fatty liver.

Citation: “Thrap3 promotes nonalcoholic fatty liver disease by suppressing AMPK-mediated autophagy,” authored by Hyun-Jun Jang, Yo Han Lee, and others, published on 32 July 2023 in Experimental & Molecular Medicine. DOI: 10.1038/s12276-023-01047-4

The research received support from the Korea Research Foundation under the Ministry of Science and ICT, National Mouse Phenotype Analysis Group (KMPC), and the UNIST Future Lead Project. Professors Jang Hyun Choi and Sung Ho Park acted as the main corresponding authors of the study, with Dr. Hyun-Jun Jang and Dr. Yo Han Lee from the Department of Biological Sciences at UNIST being among the co-authors.

Frequently Asked Questions (FAQs) about Thrap3 NAFLD treatment

More about Thrap3 NAFLD treatment

• Emerging Therapeutic Strategy Against NAFLD
• Thrap3 and Fat Metabolism in NAFLD
• UNIST’s Breakthrough on Liver Disease
• The Role of AMPK in NAFLD
• Non-Alcoholic Fatty Liver Disease Research
• Understanding Autophagy in Liver Disease