Scientists Identify a Potential Therapeutic Target for One of the Most Common Liver Diseases

The findings were published in the journal Metabolism. The researchers investigated a protein called ENT1, which transports small molecules known as nucleosides across cell membranes. These molecules are involved in various cellular processes. The scientists focused particularly on adenosine, which plays a role in regulating inflammation and cellular responses to stress.

MASLD develops in association with metabolic disorders, including obesity, and is characterized by excessive fat accumulation in the liver. In severe cases, the disease can progress to advanced fibrosis and liver cancer. However, the mechanisms underlying its development are not yet fully understood.

In experiments involving mice, the researchers compared animals with and without the ENT1 protein. They found that mice lacking ENT1 had lower levels of adenosine in the liver, along with reduced fat accumulation, inflammation, and fibrosis. These mice also showed improved glucose tolerance and increased insulin sensitivity. This suggests that ENT1 may affect not only liver health but also metabolism throughout the body.

The researchers also analyzed liver biopsies from patients and examined gene activity data. They found that ENT1 expression changed as the disease progressed. Expression levels were elevated in the early stages but declined as the disease advanced. The authors suggest that increased ENT1 activity in the early stages may promote the transport of adenosine into liver cells, contributing to pathological changes.

Among patients with early-stage MASLD, higher ENT1 expression in the liver was also associated with elevated insulin levels and a higher HOMA-IR index, a measure used to assess insulin resistance.