byUniversity of Zurich

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Long-term exposure to fine air pollution can impair metabolic health by disrupting the normal function of brown fat in mice. Astudyco-led by the University of Zurich shows that this occurs through complex changes in gene regulation driven by epigenetic mechanisms. The results demonstrate how environmental pollutants contribute to the development of insulin resistance and metabolic diseases.

There is growing evidence thatair pollutionis not just harmful to our lungs and heart, but also plays a significant role in the development of metabolic disorders likeinsulin resistanceand type 2 diabetes.

A new study co-led by Francesco Paneni, professor at the Center for Translational and Experimental Cardiology of the University of Zurich (UZH) and the University Hospital Zurich (USZ), and Sanjay Rajagopalan, professor at the Case Western Reserve University, Cleveland, now sheds light on the topic. The paper is published in the journalJCI Insight.

The researchers aimed to better understand how long-term exposure to fine air pollutants might affect the body's ability to regulate blood sugar and maintainmetabolic health. They focused on a specific type of pollution known as PM2.5, which refers to tiny airborne particles smaller than 2.5 micrometers that can be inhaled deeply into the lungs.

For their investigation, the researchers exposedlaboratory miceto either filtered air or concentrated PM2.5for six hours a day, five days a week, over a period of 24 weeks. This setup was designed to closely mimic chronic urban exposure in humans.

Particular attention was paid tobrown adipose tissue, a special type of fat that helps the body generate heat and burn calories, and therefore plays a key role in energy balance andglucose metabolism. After the exposure period of about five months, the mice that had inhaled PM2.5showed signs of disrupted metabolism, including impaired insulin sensitivity.

Further examination revealed that the function of brown fat had been significantly altered. "In particular, we found that the expression of important genes in brownadipose tissuewhich regulate its ability to produce heat, process lipids and handle oxidative stress were disturbed. These changes were accompanied by increased fat accumulation and signs of tissue damage and fibrosis within the tissue," says Paneni.

The researchers then examined the underlying mechanisms driving these changes. They found that air pollution had triggered significant changes in the regulation of DNA in brown fat cells.

This included modifications in DNA methylation patterns and changes in how accessible certain genes were for being turned on or off—a process known as chromatin remodeling. These epigenetic changes affect how cells function by regulating gene activity without altering the genetic code itself.

Two enzymes were identified as main drivers of this process: HDAC9 and KDM2B. These enzymes are involved in modifying histones, the proteins around which DNA is wrapped. They were found to bind to specific regions of the DNA in brown fat cells of the mice exposed to PM2.5, leading to a reduction in key chemical tags, or methyl groups, that normally promote gene activity.

"When these enzymes were experimentally suppressed, brown fat function improved, whereas increasing their activity led to further declines in metabolism," Paneni adds.

The study shows that long-term exposure to fine air pollution can impair metabolic health by disrupting the normal function of brown fat. This occurs through complex changes ingene regulationcontrolled by epigenetic mechanisms.

"Our findings help explain howenvironmental pollutantslike PM2.5contribute to the development of insulin resistance and metabolic disease, and they point to potential new targets for prevention or treatment," says Paneni.

More information: Rengasamy Palanivel et al, Air pollution modulates brown adipose tissue function through epigenetic regulation by HDAC9 and KDM2B, JCI Insight (2025). DOI: 10.1172/jci.insight.187023 Journal information: JCI Insight

Provided by University of Zurich