Scientists have pinpointed a crucial enzyme that shows promise in shielding the liver from the escalating damage associated with fatty liver disease, potentially paving the way for new treatments.
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease, affects an estimated 100 million people in the U.S. While many cases remain stable, a significant portion, around 20% to 25%, can progress to a more severe form called metabolic dysfunction-associated steatohepatitis (MASH). MASH is characterized by inflammation, cell damage, and scarring alongside excess liver fat, and current treatments are limited, often focusing on lifestyle changes and damage limitation.
The research, a preclinical study published in Nature Metabolism, identified that levels of an enzyme called UBE2N decrease in liver cells as MASLD advances to MASH. "The UBE2N enzyme appears to protect the liver from the inflammation and damage associated with MASH by helping remove damaged mitochondria and supporting the breakdown of fat," explained Dr. Ekihiro Seki, a professor at Cedars-Sinai and co-lead author of the study. "When levels of the enzyme fell, we saw more damaged cells and injury to the liver."
Intriguingly, when researchers boosted UBE2N levels back to normal in laboratory mice with the condition, they observed a notable reduction in fat accumulation, inflammation, and scarring. This suggests that UBE2N could be a valuable target for therapies aimed at preventing MASLD from progressing to MASH.
"The identification of this enzyme's role in regulating mitochondria in the liver is an important advance in understanding steatotic liver disease," commented Dr. Shelly Lu, another senior author from Cedars-Sinai. "Future studies can test whether enhancing this protective pathway can complement existing treatments, identify patients most likely to benefit and lead to new therapeutic approaches for preventing advanced disease."
