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Research shows how estrogen protects against fatty liver health news

New research from Sweden’s Karolinska Institutet shows how estrogen protects against MASLD, a fatty liver disease that has developed rapidly during the obesity epidemic. The study, published in the journal Molecular Systems Biology, shows how a new drug under development could be the future treatment for fatty liver disease and liver cancer.

Since last year, fatty liver due to obesity (and not excess alcohol consumption) is known as MASLD (metabolic dysfunction-associated steatotic liver disease). According to previous studies, one in three adults suffers from some degree of MASLD, which in worst cases can lead to cirrhosis and liver cancer.
Women are protected until menopause.

However, the disease is very unevenly distributed between the sexes, with a large majority of affected individuals being male.

“Women have a natural protection until menopause due to the female sex hormone estrogen,” explains Claudia Kutter, senior researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, who led the study.

Although female protection has been known for some time, the mechanism behind the protective effect has been less clear. Now Claudia Kuter’s research team may have found the answer.
Through genetic analysis of mice of both sexes fed a high-fat diet, with some male mice also receiving estrogen, the researchers were able to identify a key protein in the development of fatty liver.
The protein, called TEAD1, has been shown to play an overall role in regulating how liver cells absorb fat. Blocking TEAD1 protects liver cells from harmful fat accumulation. Mice receiving estrogen treatment had lower TEAD1 activity and less fat accumulation in the liver.

New drug under development

In the next step, the researchers tested blocking TEAD1 in human liver cells with similar results. That it was possible at all was, of course, a bit of luck.
“It turned out that a pharmaceutical company was developing an anti-cancer drug that blocks TEAD1, which allowed us to test our hypothesis,” says Claudia Kutter.
The fact that TEAD1 is involved in cancer doesn’t worry him, quite the opposite.

“Since TEAD protein activity is elevated in cancer, blocking TEAD at an early stage may also be positive from a cancer perspective,” she says. “Patients with liver cancer are currently diagnosed very late. If this drug is given at an early stage to protect patients from fatty liver, hopefully it can also prevent the development of liver cancer.”

will be tested on humans

The pharmaceutical company will now begin clinical trials of the drug as a defense against fatty liver disease, while Claudia Kutter’s research team will continue researching more ways to combat the disease.
“We want to focus on how to find the disease earlier and identify new treatment targets,” she says. “Different patients may need different procedures depending on their gender and hormonal status.”

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