A new multicenter study highlights the potential of the UBE2N enzyme in halting the progression of metabolic dysfunction-associated steatohepatitis (MASH), a serious complication of fatty liver disease. According to the American Liver Foundation, approximately 100 million people in the United States live with metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease. Of these individuals, between 20% and 25% develop MASH, characterized by excess liver fat, inflammation, cell injury, and scarring.
Currently, there is no cure for MASH, and treatment largely relies on lifestyle modifications and interventions to prevent further liver damage. While some medications are available, therapeutic options remain limited. Earlier research has implicated damaged mitochondria—the energy-producing structures within cells—in the development of the disease. The new findings from Cedars-Sinai researchers indicate that levels of the UBE2N enzyme decrease in liver cells as MASH advances.
“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,” said Ekihiro Seki, MD, PhD, a professor of Medicine and Biomedical Sciences at Cedars-Sinai and co-corresponding author of the study. “When levels of the enzyme fell, we saw more damaged cells and injury to the liver.”
To test the enzyme’s protective effects, the researchers restored UBE2N to normal levels in the livers of laboratory mice. The intervention resulted in significant reductions in fat accumulation, inflammation, and scarring. These results suggest that targeting UBE2N could be a viable strategy for preventing MASLD from advancing to MASH.
“The identification of this enzyme’s role in regulating mitochondria in the liver is an important advance in understanding steatotic liver disease,” said Shelly Lu, MD, the Women’s Guild Chair in Gastroenterology and director of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai. She added that future studies should explore whether enhancing this protective pathway can complement existing treatments and identify patients most likely to benefit.
The study involved additional authors from Cedars-Sinai, including Michitaka Matsuda, So Yeon Kim, Takashi Tsuchiya, and Yoon Seok Roh. Collaborating researchers included Feng Wang, Jin Lee, Jeong-Su Park, Meizhou Huang, Hwan Ma, Guoyan Sui, Xufeng Wu, Haram Lee, Soohwan Oh, Hanseul Park, Key-Hwan Lim, Chun-Woong Park, Sang-Bae Han, Jin Tae Hong, and Michael Karin.
Funding for the research was provided by several organizations, including the National Research Foundation of Korea, the Regional Innovation System & Education (RISE) programme of Chungbuk, the American Association for the Study of Liver Diseases, the San Diego Digestive Diseases Research Center, the National Institutes of Health, and the National Natural Science Foundation of China.
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