Home Medizin Schlüsselprotein zum Schutz von Frauen vor einer Fettlebererkrankung

Schlüsselprotein zum Schutz von Frauen vor einer Fettlebererkrankung

von NFI Redaktion

Recent research from the Karolinska Institute in Sweden reveals how estrogen protects against MASLD, a fatty liver disease that has dramatically increased during the current obesity epidemic. The study, published in Molecular Systems Biology, shows how a new drug in development could be a future treatment for fatty liver disease and liver cancer.

The global obesity epidemic has led to a dramatic rise in fatty liver, a disease where excess fat is stored in liver cells when it doesn’t fit into fat cells. Since last year, a fatty liver due to obesity (and not excessive alcohol consumption) has been known as MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease). Previous studies suggest that up to a third of adults are affected by MASLD, which can progress to liver cirrhosis and liver cancer in severe cases.

Women are Protected Until Menopause

However, the distribution of the disease between genders is very uneven, with the vast majority of those affected being men.

„Women have a natural protection from the female sex hormone estrogen until menopause,“ explains Claudia Kutter, lead researcher in the Department of Microbiology, Tumor, and Cell Biology at the Karolinska Institute who led the study.

Although female protection has been known for some time, the mechanism behind this protective effect has been less clear. Now, Claudia Kutter’s research team may have found the answer.

Through genetic analyses of mice of both sexes receiving high-fat diets, with some male mice also receiving estrogen, the researchers identified a key protein in the development of fatty liver.

It was found that the protein called TEAD1 plays a general role in regulating fat uptake by liver cells. Blocking TEAD1 protected the liver cells from harmful fat accumulation. Mice receiving estrogen treatment had lower TEAD1 activity and less fat accumulation in the liver.

New Drug in Development

In the next step, the researchers tested the blocking of TEAD1 in human liver cells with the same result. However, the fact that this was even possible was a bit of luck.

„It turned out that a pharmaceutical company is developing a cancer drug that blocks TEAD1, which allowed us to test our hypothesis,“ says Claudia Kutter.
She is not concerned that TEAD1 is also involved in cancer; in fact, quite the opposite.

„Since TEAD protein activity is increased in cancer, blocking TEAD in the early stages could also be positive from a cancer perspective,“ she says. „Today, liver cancer patients are often diagnosed very late. If this drug is administered early to protect against fatty liver, hopefully the development of liver cancer can also be prevented.“

Testing in Humans

The pharmaceutical company will now begin clinical trials with the drug for protection against fatty liver disease, while Claudia Kutter’s research team will continue to explore other ways to combat the disease.

„We want to focus on detecting the disease earlier and identifying new treatment targets,“ she says. „Different approaches may be necessary for different patients depending on gender and hormonal status.“

Source:

Journal Reference:

Sommerauer, C., et al. (2024) Estrogen Receptor Activation Alters TEAD1 Gene Expression to Alleviate Liver Steatosis. Molecular Systems Biology. doi.org/10.1038/s44320-024-00024-x.

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