New findings from the Karolinska Institutet in Sweden reveal the protective effects of estrogen against MASLD, a fatty liver disease that has become prevalent during the rise of obesity. The study, published in the journal Molecular Systems Biology, highlights the potential of a newly developed medication to serve as a treatment for fatty liver disease and liver cancer in the future.
The rise of obesity worldwide has led to a significant rise in fatty liver, a condition where excess fat is stored in liver cells when it cannot be accommodated in fat cells.
Over the past year, a condition known as MASLD (metabolic dysfunction-associated steatotic liver disease) has been identified as fatty liver caused by obesity rather than excessive alcohol intake. Previous studies have indicated that up to one-third of adults are impacted by MASLD to some extent, and in severe cases, it can progress to cirrhosis and liver cancer.
Nevertheless, there is a significant disparity in the distribution of the disease among genders, with a vast majority of those affected being males.
"Women have a natural protection until menopause due to the female sex hormone oestrogen," explains Claudia Kutter, senior researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet who led the study.
While the concept of women's protection has been recognized for a while, the exact mechanism responsible for this protective effect has remained uncertain. However, Claudia Kutter's research team may have recently discovered the answer.
Researchers were able to identify a crucial protein involved in the development of fatty liver by genetically analyzing mice of both genders who were fed a high-fat diet. Some of the male mice were additionally given estrogen.
The protein known as TEAD1 was discovered to have a significant impact on the regulation of fat absorption in liver cells. When TEAD1 was blocked, it prevented the harmful buildup of fat in the liver. Mice that were treated with oestrogen exhibited reduced TEAD1 activity and experienced less fat accumulation in their livers.
The researchers proceeded to test the inhibition of TEAD1 in human liver cells in the following stage, obtaining the same outcome. However, it was fortunate that this was even feasible.
"It turned out that a pharmaceutical company is developing an anti-cancer drug that blocks TEAD1, which allowed us to test our hypothesis," says Claudia Kutter.
She is not worried about the fact that TEAD1 is also implicated in cancer; on the contrary, it has the opposite effect on her.
"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," she says. "Patients suffering from liver cancer are currently diagnosed very late. If the patient is given this drug early in the process to protect against fatty liver, it can hopefully also prevent the development of liver cancer."
The drug will undergo clinical trials by the pharmaceutical company to determine its effectiveness in preventing fatty liver disease. Meanwhile, Claudia Kutter's research team will continue their investigation into additional approaches for addressing the disease.
"We want to focus on how to find the disease earlier and identifying new treatment targets," she says. "Different approaches may be needed for different patients depending on their gender and hormonal status."
