Long-term exposure to fine particulate matter can have lasting detrimental effects on metabolic health, thereby contributing to diseases such as obesity and type 2 diabetes. A new study led by Professor Francesco Paneni from the University of Zurich (UZH) and University Hospital Zurich (USZ), along with Professor Sanjay Rajagopalan from Case Western Reserve University in Cleveland, shows that tiny air particles (PM2.5) disrupt the function of brown adipose tissue in mice. This occurs through epigenetic changes in gene regulation, which promote insulin resistance and tissue damage. The findings, published in JCI Insight, underscore the far-reaching health risks of air pollution beyond lung and heart diseases.
Chronic exposure in an animal model
The researchers investigated how long-term exposure to PM2.5 – particles smaller than 2.5 micrometers that penetrate deep into the lungs and originate from sources such as car exhaust, industrial plants, heating systems, construction sites, or wildfires – affects blood sugar levels and energy metabolism. In one experiment, they exposed laboratory mice for 24 weeks to either purified air or concentrated PM2.5 for six hours daily, five days a week. This scenario simulates chronic exposure in urban environments in humans.
Particular attention was paid to brown adipose tissue, which is essential for heat generation, calorie burning, and glucose metabolism. After the five-month exposure period, the exposed mice showed metabolic disturbances, including impaired insulin sensitivity. "We found that the expression of key genes in brown adipose tissue, which regulate its ability to produce heat, process lipids, and cope with oxidative stress, was disrupted. These changes were accompanied by increased fat accumulation, tissue damage, and fibrosis," explains Paneni.
Epigenetic mechanisms as the key
The underlying processes were analyzed in detail: fine particulate matter exposure led to significant epigenetic changes in brown fat cells, including altered DNA methylation patterns and chromatin remodeling – processes that control gene activity without changing the DNA code. Two enzymes, HDAC9 and KDM2B, played a central role: they bind to specific DNA regions and reduce methylation groups that normally promote gene activity. "When we experimentally suppressed these enzymes, brown adipose tissue function improved, while increasing their activity further worsened metabolism," adds Paneni.
Implications for prevention and therapy
The study clarifies how environmental toxins like PM2.5 trigger insulin resistance and metabolic diseases by damaging brown adipose tissue. "Our findings explain how fine particulate matter contributes to the development of insulin resistance and metabolic diseases, and point to new targets for prevention or treatment," emphasizes Francesco Paneni. HDAC9 and KDM2B could serve as therapeutic targets, for example, through inhibitors, to protect metabolic health in exposed populations.
Public Health and Environmental Protection
The results have far-reaching consequences for public health: In highly polluted regions, fine particulate matter could be a significant risk factor for the increase in obesity and diabetes. They underscore the urgency of measures to reduce PM2.5 emissions and call for interdisciplinary approaches that incorporate environmental factors into the prevention of metabolic diseases. The study opens new avenues for personalized therapies that could reverse epigenetic changes.
Reference:
Rengasamy Palanivel, Jean-Eudes Dazard et al. Air pollution impairs brown adipose tissue function through epigenetic regulation of HDAC9 and KDM2B. JCI Insight, September 23, 2025. DOI: https://doi.org/10.1172/jci.insight.187023
Contact:
Francesco Paneni, Center for Translational and Experimental Cardiology, University of Zurich and University Hospital Zurich.
Further information: https://www.news.uzh.ch/en/articles/media/2025/air-pollution-fat-metabolism.html
This research marks a significant step in linking environmental pollution and metabolic diseases and could contribute to more effective strategies against the global pandemic of diabetes and obesity.
