Microplastics Linked to Worsening Fatty Liver Disease

University of Oklahoma

OKLAHOMA CITY – Microplastics – minuscule pieces of plastic broken down from larger plastic waste – are a growing concern for human health, especially for the liver. A study from the University of Oklahoma, published today in Science Advances, demonstrates that a common type of microplastics is particularly harmful to the liver under high-fat dietary conditions.

The study, conducted in mice, found that blood markers of liver injury were more than twice as high in animals exposed to microplastics while consuming a high-fat diet compared with animals exposed to the same particles while consuming a standard diet. The study focused on the most common type of plastic, polyethylene, which is found in materials like plastic bags and milk jugs.

"Exposure to microplastics is inevitable. We inhale them, ingest them and they are on our skin," said Tae Gyu Oh, Ph.D., who led the study and is an assistant professor of oncology science in the OU College of Medicine. "Numerous studies have shown the presence of microplastics in our bodies, but we wanted to investigate the effects of microplastics in the setting of a high-fat, high-cholesterol diet, which has also been shown to harm the liver. We expected to see a synergistic effect between the diet and microplastics, and we did."

In the study, researchers administered microplastics in equal amounts to the mice over eight weeks. Some of the mice were fed a standard diet, and others were fed a diet designed to model metabolic dysfunction-associated steatohepatitis (MASH), a serious form of fatty liver disease.

To better understand what was happening inside the liver, Oh and his team examined the liver tissue using a variety of technologies that increasingly "zoomed in" on the cells. Each technology showed liver damage, but the highest resolution was provided through spatial transcriptomics. The research team's use of the technology in this context is believed to be a first.

Whereas traditional technology (such as bulk transcriptomics) showed a single, averaged reading of millions of cells, spatial transcriptomics pinpointed exactly where the damage occurred.

"This high-resolution view helped us identify specific 'hot spots' of liver damage at the single-cell level that would have been impossible to detect using traditional approaches," Oh said.

The study also identified a gene regulator known as PPAR-alpha as playing a key role in the liver's response to microplastic exposure. PPAR-alpha, a protein inside the cells that controls how the body breaks down and uses fat for energy, influences a gene called Anxa2, which plays a role in tissue repair.

"These findings suggest that microplastics may affect some of the liver's natural defense and repair mechanisms," Oh said. "Understanding this relationship may point us toward new ways to protect liver health."

Although the research was conducted in mice and additional research is needed to determine whether the same effects occur in humans, the study establishes a framework for understanding how microplastics may contribute to liver disease.

"Microplastics are now part of our everyday environment, but we are still learning how they affect the body," Oh said. "By gaining such a detailed look at the liver, we were able to see specific regions where microplastic exposure triggered inflammation and altered important biological pathways. These findings provide new clues about how environmental exposures may contribute to liver disease and point to areas for future investigation."

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