Lyz-IFNγR2−/− Mice are rescued from progression of hepatic steatosis to MASH. Credit: Nature Communications (2024). DOI: 10.1038/s41467-024-49633-y
Research from the lab of Jason Kim, Ph.D., professor of molecular medicine and medicine, has identified a novel pathway in the progression of metabolic liver disease that could be targeted for potential therapies.
The results, published in Nature Communicationsdescribe how interferon-γ, a circulating protein that is higher in obese people, causes inflammation. By blocking this pathway, Dr. Kim and colleagues were able to protect animal models from developing metabolic dysfunction-associated steatohepatitis (MASH).
“The liver can normally store fat, but that’s when inflammation develops,” Kim says. “That’s what leads to the progression of this pathogenic disease. We think we’ve found a way to prevent that from happening.”
MASH, the most severe form of metabolic liver disease, is characterized by inflammation, insulin resistance, and scarring of the liver (fibrosis). Thirty percent of people over the age of 60 and three out of four obese people have metabolic liver disease, representing an urgent global health problem. Despite its prevalence, only one drug has recently been approved by the Food and Drug Administration to treat it.
“People with MASH are normally advised to change their diet and exercise. However, this discovery could help us prevent the disease from progressing without patients having to make drastic lifestyle changes,” Kim said.
Proposed model of the IFNγ-IL12 axis regulating hepatic insulin resistance and MASH. Credit: Nature Communications (2024). DOI: 10.1038/s41467-024-49633-y
He explained that it has long been known that inflammation develops during metabolic liver disease, but it is not understood how this inflammation occurs and how it affects liver cells.
Using new transgenic mice, the research team showed that blocking these macrophages or immune cells and their communication with liver cells reduces inflammation and the progression of metabolic liver disease in obesity, a first according to Kim.
“Understanding the role of inflammation in the liver and identifying molecular targets to block this process will lead to new therapies to treat the epidemic population,” Kim said.
The next step is to identify the nature of the communication between liver macrophages and hepatocytes or liver cells and how this communication can be modified to stop the progression of metabolic liver disease, Kim said.
More information:
Randall H. Friedline et al, The IFNγ-IL12 axis regulates intercellular communication in steatotic liver disease associated with metabolic dysfunction, Nature Communications (2024). DOI: 10.1038/s41467-024-49633-y
Provided by the University of Massachusetts Medical School
Quote:New pathway could lead to potential treatment for metabolic liver disease (2024, August 30) retrieved August 30, 2024 from
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