Complexity (NAFLD) that affects nearly one-third of non-alcoholic fatty liver disease (NAFLD) worldwide requires in-depth understanding of its underlying causes. This disease is often associated with modern lifestyle choices such as sedentary behaviors and a high-fat diet, which is a growing public health issue. The key to developing effective treatments is to uncover its molecular roots. The forefront of this exploration is the pioneering work of Professor Jung Weon Lee and his team. Their focus on the key protein TM4SF5 elucidates its role in this complex disease. Their research on Iscience provides new hope for changing our approach to managing and treating NAFLD and its more severe non-alcoholic steatohepatitis (NASH).
In their innovative research, Professor Jung Weon Lee and his team, HWI Young Kim from EWHA WOMANS University, revealed fundamental insights into the increasingly common problems of non-alcoholic fatty liver disease (NAFLD). Their work, published in the form of varicose veins, centered on a membrane protein called TM4SF5, shows its critical role in the development of NAFLD and its more severe non-alcoholic steatohepatitis (NASH).
“For mice with hepatocytes TM4SF5 overexpression, it was unexpected, and during those times that should be sleepy, it was extra food.” Professor Li also explained their core of the study, noting that “the presence of TM4SF5 in hepatocytes may lead to unhealthy changes in the liver due to abnormal eating habits, increased levels of hormone proteases that stimulate appetite stimulation, and changes in SPP-1 and SPP -1 changes/OPN levels, even in short-term conventional or high-fat diets. “This insight highlights the significant impact of TM4SF5 on liver health, beyond simple dietary factors.
The team used a unique approach involving specially modified mice to study the effects of TM4SF5. These mice were changed to excessive or completely free of TM4SF5 protein in their hepatocytes. This design allows for in-depth comparison of its effects under different dietary conditions. The researchers closely monitored the dietary patterns associated with their active and rest periods to gain insight into abnormal dietary behaviors associated with TM4SF5. They also conducted detailed examinations of liver tissue and blood samples, focusing on liver health indicators and hormones that affect appetite and metabolism at the early stages of NAFLD characteristics.
Professor Lee further elaborated on their findings: “Mices with elevated TM4SF5 levels exhibit abnormal dietary patterns, especially eating more during the usual rest period. This unusual behavior is associated with higher levels of TM4SF5 Expression is associated with respiratory hormones. “This finding is crucial to link TM4SF5 to the development of chronic liver diseases such as NASH.
The study also included human subjects and analyzed samples of NAFLD patients. Professor Li discussed the effects of human health and noted: “The respirin levels in the blood appear to match the levels of TM4SF5 in the liver due to the small number of samples.” This observation suggests that the possible progression between TM4SF5, APELIN levels, BMI and NAFLD There is a relationship.
In summary, Professor Li’s research provides important insights into the role of TM4SF5 in causing NAFLD and NASH through abnormal dietary behavior and hormonal changes. These groundbreaking findings open up new possibilities for treatment, potentially changing the way we deal with liver diseases affected by dietary habits, and in addition to changing the anti-TM4SF5 strategy.
Journal Reference
Pinanga YD, Lee HA, Shin EA, Lee H, Pyo KH, Kim Je, Lee EH, Kim W, Kim S, Kim S, Kim HY, Lee JW. TM4SF5-mediated abnormal food endurance behavior and Apelin expression promote the characteristics of non-alcoholic fatty liver disease. Iscience. August 14, 2023; 26 (9): 107625. doi:
About the Author
Dr. Jung Weon Lee He is a professor in the Department of Pharmacy, School of Pharmacy, Seoul National University, Republic of Korea. He received his Ph.D. In 2000, a degree in Pharmacology from the University of North Carolina, North Carolina. In 2001, he returned to South Korea to serve as an assistant professor at the SNU Medical School in South Korea. In 2009, he moved to the pharmacy department at SNU and is now a full professor. His research focuses on how cellular function occurs at the molecular level, including morphological changes and multiple functions, especially under the control or influence of the tetrassin protein TM4SF5 protein in control or in vitro animal models. Progress. As a membrane protein induced by inflammatory regulators in pathological conditions, TM4SF5 forms a huge protein-protein complex called TM4SF5-enhanced microdomain (T5erm) used to act as a membrane signaling hub. The TM4SF5-mediated effect on cellular function can lead to the development of non-alcoholic and chronic liver disease. He therefore of course also explored the development of anti-TM4SF5 reagents (such as small molecules and therapeutic monoclonal antibodies) to prevent TM4SF5-mediated liver diseases, including non-alcoholic steatohepatitis, fibrosis and cancer. In the past few days, his research team has focused on exploring how TM4SF5 acts as an immune checkpoint and whether anti-TM4SF5 reagents can become a new approach to immunotherapy for chronic liver disease (OrcID: Lab Homepage: Lab Homepage:
