In a recent breakthrough at Karolinska Institutet, scientists have uncovered how the female sex hormone estrogen plays a crucial role in defending against MASLD, a type of fatty liver disease increasingly common due to the global obesity crisis.
Their findings, published in Molecular Systems Biology, not only deepen our understanding of this condition but also point towards a promising new treatment that could benefit those suffering from fatty liver disease and potentially prevent liver cancer.
MASLD, or metabolic dysfunction-associated steatotic liver disease, has become a widespread health concern, affecting up to one in three adults.
This condition arises when excess fat, unable to be stored in fat cells, accumulates in the liver, potentially leading to severe outcomes like cirrhosis and liver cancer.
Interestingly, this disease affects men significantly more than women, a discrepancy believed to be due to the protective effects of estrogen up until menopause.
The mystery behind estrogen’s protective shield has puzzled scientists for years, but the team led by Claudia Kutter at Karolinska Institutet may have finally cracked the code.
By studying genetic data from mice on a high-fat diet and administering estrogen to some of the males, they identified a key player: a protein called TEAD1.
This protein is crucial in managing how liver cells deal with fat, and its inhibition could prevent the dangerous build-up of fat in the liver. Indeed, the mice treated with estrogen showed reduced TEAD1 activity and, consequently, less liver fat accumulation.
The team’s breakthrough didn’t stop with mice. They moved on to human liver cells, achieving similar success in blocking TEAD1 and preventing fat accumulation.
As luck would have it, this discovery coincided with the development of an anti-cancer drug by a pharmaceutical company, which targets TEAD1.
This serendipitous overlap allowed Kutter’s team to test their hypothesis with an existing compound, opening the door to potential new therapies for MASLD and liver cancer.
The connection between TEAD1 and cancer adds an intriguing layer to the research. Since TEAD proteins often have increased activity in cancer, blocking them not only helps in preventing fatty liver disease but might also offer early-stage cancer protection.
This dual benefit is particularly important considering the late diagnosis common in liver cancer patients. By using this drug early, there’s hope for both preventing fatty liver disease and halting the progression to liver cancer.
Clinical trials for the anti-TEAD1 drug as a treatment for fatty liver disease are on the horizon, marking a significant step towards tackling this growing health issue. Meanwhile, Kutter’s team is set on further exploring how to detect MASLD earlier and identify additional treatment targets.
Given the disease’s varied impact based on gender and hormonal status, a one-size-fits-all approach might not be sufficient. This research opens up a new avenue for personalized treatments, promising a brighter future for those at risk of fatty liver disease and its severe consequences.
If you care about wellness, please read studies about how ultra-processed foods and red meat influence your longevity, and why seafood may boost healthy aging.
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The research findings can be found in Molecular Systems Biology.
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