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March 8, 2024 – Fatty liver disease, a condition characterized by the accumulation of fat in liver cells, has surged in prevalence alongside the global obesity epidemic. Now, a groundbreaking study from Karolinska Institutet sheds light on a promising avenue for treatment, offering hope to millions affected by this debilitating disease.
Published in Molecular Systems Biology, the study unveils how oestrogen, the female sex hormone, acts as a natural shield against metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as fatty liver due to obesity. Led by senior researcher Claudia Kutter from the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet, the research elucidates the protective mechanism of oestrogen and identifies a key protein, TEAD1, involved in fat accumulation in liver cells.
According to Kutter, women are inherently protected from MASLD until menopause due to oestrogen. However, the precise mechanism underlying this protective effect has remained elusive until now. Through genetic analyses in mice fed a high-fat diet, the research team uncovered TEAD1’s pivotal role in regulating fat absorption in liver cells. Blocking TEAD1 effectively shielded liver cells from harmful fat accumulation, with male mice receiving oestrogen treatment exhibiting lower TEAD1 activity and reduced fat accumulation in the liver.
Excitingly, the study’s findings paved the way for the development of a potential treatment for MASLD and liver cancer. A pharmaceutical company currently developing an anti-cancer drug that targets TEAD1 provided the opportunity to test the researchers’ hypothesis. Kutter emphasizes that despite TEAD1’s involvement in cancer, early intervention with TEAD1-blocking drugs holds promise for preventing not only MASLD but also liver cancer.
The next phase of this research involves clinical trials of the TEAD1-blocking drug to assess its efficacy in protecting against fatty liver disease. Concurrently, Kutter’s team will continue investigating novel approaches to combat MASLD, recognizing the need for tailored treatments based on patients’ gender and hormonal status.
Funded by prestigious organizations including the Knut and Alice Wallenberg Foundation and the Swedish Research Council, the study underscores the importance of collaborative efforts in advancing medical research. While some authors declare affiliations with pharmaceutical companies, conflicts of interest were not reported in relation to this study.
With promising developments on the horizon, this research offers a glimmer of hope for individuals battling fatty liver disease and underscores the potential of targeted therapies in improving health outcomes for millions worldwide.
