New analysis reveals that the Thrap3 protein aggravates NAFLD by disrupting fats metabolism within the liver, suggesting that concentrating on Thrap3 might result in new therapies for the illness.
A breakthrough examine, collectively led by Professor Jang Hyun Choi and Professor Sung Ho Park from the Department of Biological Sciences at UNIST has recognized a key issue implicated within the development of non-alcoholic fatty liver illness (NAFLD), which is usually triggered by weight problems. The researchers discovered {that a} protein referred to as Thrap3, which is related to thyroid hormone receptors, considerably worsens NAFLD. It does so by suppressing the exercise of adenosine monophosphate-activated protein kinase (AMPK), a key regulator of fats metabolism within the liver.
Significance and Mechanism of Thrap3 in NAFLD
NAFLD encompasses varied metabolic ailments similar to fatty hepatitis and cirrhosis ensuing from extreme fats accumulation. Despite its prevalence, efficient therapies for NAFLD have been restricted. However, this groundbreaking analysis sheds gentle on potential therapeutic approaches.
A breakthrough examine, collectively led by Professor Jang Hyun Choi and Professor Sung Ho Park from the Department of Biological Sciences at UNIST has recognized an essential issue concerned within the growth of non-alcoholic fatty liver illness (NAFLD) attributable to weight problems. Credit: UNIST
Through animal experiments performed on rats, the analysis crew demonstrated that Thrap3 immediately binds to AMPK throughout the liver. This interplay prevents AMPK from translocating from the nucleus to the cytoplasm and impairs autophagy—a course of essential for breaking down triglycerides and lowering levels of cholesterol. In essence, inhibiting Thrap3 expression presents a promising avenue for successfully treating NAFLD.
Research Impact and Future Prospects
“We have encountered significant challenges while developing treatment strategies for non-alcoholic fatty liver disease. However, our discovery of the Thrap3 gene provides us with an effective method to tackle this condition,” commented Professor Choi.
Schematic diagram of the mechanism by which Thrap3 impacts NAFLD via translocation of AMPK. Credit: UNIST
Additionally, it was confirmed that suppressing Thrap3 expression successfully improves non-alcoholic steatohepatitis—an inflammatory illness stemming from fatty liver.
Reference: “Thrap3 promotes nonalcoholic fatty liver disease by suppressing AMPK-mediated autophagy” by Hyun-Jun Jang, Yo Han 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, 32 July 2023, Experimental & Molecular Medicine.
DOI: 10.1038/s12276-023-01047-4
Supported by funding from the Korea Research Foundation below the Ministry of Science and ICT, National Mouse Phenotype Analysis Group (KMPC), and UNIST Future Lead Project. Professor Jang Hyun Choi, alongside Professor Sung Ho Park, served as corresponding authors of the paper, with Dr. Hyun-Jun Jang and Dr. Yo Han Lee from the Department of Biological Sciences at UNIST taking part as co-authors.
