A groundbreaking study led by researchers from UNIST’s Department of Biological Sciences has identified a key factor associated with the progression of non-alcoholic fatty liver disease (NAFLD), which is often triggered by obesity. The research team, led by Professors Jang Hyun Choi and Sung Ho Park, found that a protein called Thrap3 interacts with thyroid hormone receptors to significantly worsen NAFLD.
Significance and mechanism of Thrap3 in NAFLD
NAFLD encompasses a range of metabolic disorders, including steatohepatitis and cirrhosis, caused by excessive accumulation of fat in the liver. Despite the high prevalence of NAFLD, effective treatments for NAFLD remain limited. However, this groundbreaking study provides new insights and potential treatments.
Through animal experiments in rats, the team demonstrated that Thrap3 directly binds to AMPK in the liver. This interaction blocked the transfer of AMPK from the nucleus to the cytoplasm and impaired autophagy – a key process that breaks down triglycerides and lowers cholesterol levels. Essentially, inhibiting Thrap3 expression provides a promising avenue for effective treatment of NAFLD.
Research Implications and Future Prospects
Prof. Choi commented, “We have encountered great challenges in developing therapeutic strategies for NAFLD. However, the discovery of the Thrap3 gene provides us with an effective way to treat this disease.
In addition, the study confirms that inhibiting the expression of Thrap3 can effectively ameliorate NAFLD – an inflammatory disease originating from fatty liver.
Reference.
“Thrap3 promotes nonalcoholic steatohepatitis by inhibiting AMPK-mediated autophagy.”
Hyunjoon Chang, Yohan Lee, Tam Dao, Yunju Jo, Keon Woo Khim, Hye-jin Eom, Ju Eun Lee, Yi Jin Song, Sun Sil Choi, Kieun Park, Haneul Ji, Young Chan Chae, Kyungjae Myung, Hongtae Kim, Dongryeol Ryu, Neung Hwa Park, Sung Ho Park and Jang Hyun Choi.
Experimental and Molecular Medicine
DOI: 10.1038/s12276-023-01047-4
Supported by: Korea Research Foundation, Ministry of Science
Korea Research Foundation, Ministry of Science, Technology and Information Communication, Korea
National Mouse Phenotype Cell (KMPC)
UNIST Future Leaders Program
Contributors: Prof. Jang Hyun Choi
Prof. Jang Hyun Choi and Prof. Sung Ho Park are the corresponding authors of this paper, and Dr. Hyun-Jun Jang and Dr. Yo Han Lee from the Department of Biological Sciences at UNIST are the co-authors.