New research from Karolinska Institutet reveals how estrogen protects against metabolic dysfunction-associated steatotic liver disease (MASLD), a form of fatty liver disease that has surged during the global obesity epidemic. The study, published in Molecular Systems Biology, sheds light on a potential future treatment for fatty liver disease and liver cancer.
The obesity epidemic has led to a significant rise in fatty liver, a condition where excess fat is stored in liver cells instead of fat cells. Since last year, fatty liver due to obesity is known as MASLD. Research indicates that as many as one in three adults are affected by some degree of MASLD, which in severe cases can progress to cirrhosis and liver cancer.
However, the disease is disproportionately prevalent among men, with women naturally protected until menopause due to the female sex hormone estrogen. Claudia Kutter, senior researcher at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet, led the study and explains, ‘Women have a natural protection until menopause due to the female sex hormone estrogen.’
While the protective effect of estrogen in women has been recognized for some time, the underlying mechanism has been less understood. Kutter’s research team may have now uncovered the answer through genetic analyses of mice. The researchers identified a key protein, TEAD1, which plays a crucial role in regulating how liver cells absorb fat. Blocking TEAD1 protected liver cells from the harmful accumulation of fat. Mice receiving estrogen treatment exhibited lower TEAD1 activity and less fat accumulation in the liver.
Subsequent testing in human liver cells yielded similar results, and the researchers were fortunate to find that a pharmaceutical company is developing an anti-cancer drug that blocks TEAD1, enabling them to test their hypothesis. Kutter notes, ‘Since the activity of TEAD proteins is elevated in cancer, blocking TEAD at an early stage can also be positive from a cancer point of view.’
The findings offer promising insights into potential future treatments for fatty liver disease and liver cancer. Further research and development of drugs targeting TEAD1 could hold the key to addressing the rising prevalence of MASLD and its associated health risks.
