Study Reveals Mechanisms of Estrogen’s Protective Effects on Fatty Liver

Recent research from Sweden’s Karolinska Institutet sheds light on how estrogen shields against MASLD, a fatty liver disease that has surged alongside the obesity epidemic. Published in Molecular Systems Biology, the study unveils insights that could pave the way for a novel medicine to combat fatty liver disease and liver cancer.

The global rise in obesity has led to a sharp increase in fatty liver, a condition where excess fat accumulates in liver cells instead of fat cells. Referred to as MASLD (metabolic dysfunction-associated steatotic liver disease) since last year, the disease affects as many as one in three adults, with severe cases potentially progressing to cirrhosis and liver cancer.

Despite the widespread prevalence of MASLD, there’s a notable gender discrepancy, with a significant majority of affected individuals being men. Claudia Kutter, a senior researcher at Karolinska Institutet’s Department of Microbiology, Tumor, and Cell Biology, attributes this gender disparity to the natural protection conferred by the female sex hormone estrogen until menopause.

While the protective effect of estrogen in women has long been recognized, the underlying mechanism has remained elusive. However, Kutter’s research team may have unraveled this mystery. Through genetic analyses involving mice of both sexes subjected to a high-fat diet, supplemented with estrogen in some male mice, the researchers pinpointed a crucial protein implicated in fatty liver development.

Named TEAD1, this protein was found to play a pivotal role in regulating the fat absorption process in liver cells. Inhibiting TEAD1 effectively shielded liver cells from harmful fat accumulation. Mice treated with estrogen exhibited reduced TEAD1 activity and less fat accumulation in the liver.

Subsequent experiments on human liver cells yielded similar outcomes when TEAD1 was blocked. This fortuitous discovery was facilitated by a pharmaceutical company’s ongoing development of an anti-cancer drug targeting TEAD1.

Kutter is optimistic about the potential dual benefits, considering TEAD1’s involvement in cancer. By blocking TEAD1 early on, the drug could not only safeguard against fatty liver but also potentially thwart the progression to liver cancer, which is often diagnosed at advanced stages.

The pharmaceutical company plans to initiate clinical trials for the drug’s efficacy in preventing fatty liver disease, while Kutter’s team continues exploring additional avenues for combating the disease. Their focus lies on early disease detection and identifying new treatment targets, recognizing the need for tailored approaches based on patients’ gender and hormonal status.