This protective enzyme could help stop fatty liver disease from getting worse

 

A newly identified protective enzyme could offer scientists a new way to stop fatty liver disease before it causes serious liver damage. Credit: Shutterstock

Researchers co-led by Cedars-Sinai Health Sciences University have identified an enzyme that may help protect the liver from the damage that can occur as the most common form of liver disease becomes more severe. The findings, from a preclinical study published in Nature Metabolism, could eventually support new strategies for preventing serious liver injury and progression toward liver failure.

An estimated 100 million people in the U.S. have metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called nonalcoholic fatty liver disease, according to the American Liver Foundation. Roughly 20% to 25% of those affected go on to develop metabolic dysfunction-associated steatohepatitis (MASH), a more serious form of the condition in which excess liver fat is accompanied by inflammation, cell injury and scarring.

Why MASH Is Difficult to Treat

Current care mainly centers on lifestyle changes and efforts to limit additional liver damage. Although medications are available, treatment options are still limited, and there is currently no cure for MASH.

Earlier research has suggested that damaged mitochondria, the structures that produce energy for cells, may contribute to the development and progression of MASH. In the new multicenter study, Cedars-Sinai researchers found that levels of an enzyme called UBE2N decline in liver cells as the disease becomes more advanced.

"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, 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."

Restoring UBE2N Reduced Liver Damage in Mice

The researchers then restored UBE2N to normal levels in the livers of laboratory mice. After doing so, they observed reductions in fat accumulation, inflammation and scarring.

Those results suggest that UBE2N could become a potential treatment target 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. "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."

Additional Cedars-Sinai authors include Michitaka Matsuda, So Yeon Kim, Takashi Tsuchiya and Yoon Seok Roh.

Additional authors include: Feng Wang, Jin Lee, Jeong-Su Park, Meizhou Huang, Hwan Ma, Guoyan Sui, Zixiong Zhou, Xufeng Wu, Haram Lee, Soohwan Oh, Hanseul Park, Key-Hwan Lim, Chun-Woong Park, Sang-Bae Han, Jin Tae Hong and Michael Karin.

Funding: This work was supported by the National Research Foundation of Korea (grant nos. RS-2025-02273102 and RS-2025-02603096), Regional Innovation System & Education (RISE) programme of Chungbuk (grant no. 2025-RISE-11-014-03), the Pinnacle Research Award of American Association for the Study of Liver Diseases (AASLD, to J.L.), the San Diego Digestive Diseases Research Center (SDDRC) Pilot/Feasibility Grant (NIDDK P30 DK120515, to J.L.), the National Institutes of Health (grant nos. R01DK085252, R01DK138591 and R01CA301632) and the National Natural Science Foundation of China (grant no. 82404726).

Journal Reference:

1. Feng Wang, Jin Lee, Jeong-Su Park, Meizhou Huang, Hwan Ma, Guoyan Sui, Zixiong Zhou, Michitaka Matsuda, So Yeon Kim, Takashi Tsuchiya, Xuefeng Wu, Haram Lee, Soohwan Oh, Hanseul Park, Key-Hwan Lim, Chun-Woong Park, Sang-Bae Han, Jin Tae Hong, Michael Karin, Yoon Seok Roh, Ekihiro Seki. UBE2N deficiency contributes to MASH development via p62-regulated mitophagy and PANoptosis. Nature Metabolism, 2026; 8 (9): 1926 DOI: 10.1038/s42255-026-01590-0

Courtesy:

Cedars-Sinai. "This protective enzyme could help stop fatty liver disease from getting worse." ScienceDaily. ScienceDaily, 3 October 2026. <www.sciencedaily.com / releases / 2026 / 10 / 261002080020.htm>.

 

 

Your gut may be making a molecule that raises Alzheimer’s risk

 

A compound made by gut bacteria may quietly raise Alzheimer’s risk and speed cognitive decline, giving scientists a promising new treatment target. Credit: Shutterstock

A molecule made by bacteria in the digestive system may increase the risk of Alzheimer's disease and accelerate cognitive decline in people with dementia, according to new research. The finding could point scientists toward a potential treatment strategy aimed at lowering Alzheimer's risk.

Nearly a decade ago, a research team led by University of Wisconsin-Madison professors Barbara Bendlin and Federico Rey found that the mix of microorganisms living in the intestines differs between people with Alzheimer's disease and healthy individuals.

"Since then, we've been trying to figure out how this difference in the gut perhaps leads to changes in the brain," says Bendlin, a professor of medicine in the UW School of Medicine and Public Health.

A Gut Molecule With Effects Beyond the Intestines

In a recent study published in the journal Nature Communications, Bendlin, Rey and their collaborators focused on imidazole propionate (ImP), a compound produced by certain bacteria in the gut. Their findings suggest that ImP may contribute to brain changes involved in Alzheimer's disease and related forms of dementia.

ImP production varies considerably from person to person. Some people appear to generate relatively large amounts, while others produce very little.

"ImP-producing bacteria are present in a large fraction of people, but they're not very abundant in most people," says Rey, a UW-Madison professor of bacteriology. "But something we have learned over the years is that a microbe doesn't have to be abundant to have an impact on the host."

Once produced in the gut, ImP can enter the circulation and reach other parts of the body. Previous research has linked the compound to type 2 diabetes and coronary artery disease.

The new study suggests that its effects may also extend to the brain. In mice, researchers found that ImP reaching the brain increased the accumulation of abnormal beta amyloid and tau proteins, two major hallmarks associated with Alzheimer's disease.

"That process eventually results in the death of neurons, and in humans is a key feature of Alzheimer's disease," Rey says.

Higher ImP Levels Linked to Faster Cognitive Decline

The researchers then examined blood samples from almost 1,200 people enrolled in the Wisconsin Registry for Alzheimer's Prevention and studies conducted through the Wisconsin Alzheimer's Disease Research Center.

Participants with higher concentrations of ImP in their blood were much more likely to show biological markers associated with abnormal proteins and impaired neuron function in dementia.

Because the volunteers had also completed cognitive testing over time, the researchers were able to compare ImP levels with changes in thinking and memory.

"And because we have the results of cognitive tests these volunteers took over time, we can see that the people with the highest ImP levels also experienced much faster cognitive decline," Rey says.

The team also discovered a genetic variation associated with substantially higher levels of ImP in the bloodstream. About 43% of the people in the study carried this variation.

Researchers suspect the genetic difference may influence how effectively the kidneys remove ImP from the blood, affecting how much of the compound remains in circulation.

"This genetic variation has been associated with increased Alzheimer's risk in large genetic studies before, and now we may understand why it's connected," Rey says.

A Potential New Target for Alzheimer's Prevention

One of the most important possibilities raised by the findings is that ImP itself could become a target for preventing or slowing Alzheimer's disease and related dementias.

However, reducing ImP through diet alone may not be straightforward. Gut bacteria produce the compound while generating energy from histidine, an amino acid that is essential for human health and found in many foods, particularly foods rich in protein.

"Generally improving your diet would probably help," Bendlin says. "But it's not as easy as saying, 'Stop eating eggs' or 'Don't eat so much red meat.' Because you need histidine, and it's all over the place."

Rather than trying to eliminate histidine from the diet, the researchers say the discovery could eventually lead to treatments that specifically reduce ImP levels in the bloodstream.

Identifying a particular molecule and a related genetic variation gives scientists a more precise target to investigate.

"It could be just like cholesterol, where people with elevated cholesterol take a drug, a statin, that reduces their risk for heart disease," Bendlin says. "If we can find an inhibitor that can help decrease the levels of ImP in the blood, that could hopefully reduce the risk of Alzheimer's and the speed of cognitive decline for a significant number of people."

Scientists from the University of California, Los Angeles and the University of Gothenburg also contributed to the study.

This research was supported in part by grants from the Wisconsin Partnership Program and the National Institutes of Health (R01AG070973, R01AG083883, R01AG092220, R21AG089348, R01HL168493, R01DK143650 and U54HL170326) and the U.S. Department of Agriculture (WIS03073).

Journal Reference:

1. Vaibhav Vemuganti, Jea Woo Kang, Qijun Zhang, Eric R. McGregor, James R. Hilser, Ruben Aquino-Martinez, Sandra Harding, Joseph Lawrence Harpt, Katharina R. Beck, Hailey Bussan, Jessamine F. Kuehn, Yuetiva Deming, Rachel Studer, Sterling C. Johnson, Sanjay Asthana, Henrik Zetterberg, Kaj Blennow, Corinne D. Engelman, Hooman Allayee, Rozalyn M. Anderson, Tyler K. Ulland, Fredrik Bäckhed, Barbara B. Bendlin, Federico E. Rey. Gut bacterial metabolite imidazole propionate potentiates Alzheimer’s disease pathology. Nature Communications, 2026; 17 (1) DOI: 10.1038/s41467-026-74744-z

Courtesy:

University of Wisconsin-Madison. "Your gut may be making a molecule that raises Alzheimer’s risk." ScienceDaily. ScienceDaily, 3 October 2026. <www.sciencedaily.com / releases / 2026 / 09 / 260930225459.htm>.