USA: A new study has revealed that a high-fat diet can trigger asthma-like lung inflammation, first seen in mice and later confirmed in human lung tissue tests.
The research, published in
Science Translational Medicine, highlights how certain dietary fats can directly influence immune activity in the lungs, offering fresh insights into the connection between nutrition and respiratory health.
The investigation, led by Sam J. McCright from the Department of Pediatrics at the Perelman School of Medicine, University of Pennsylvania, explored how diets rich in saturated long-chain fatty acids affect the lungs’ immune environment. Resident tissue macrophages and monocytes—immune cells that help maintain healthy tissue—are known to respond to metabolic stress. However, their reaction to specific dietary components has been less clear. McCright’s team focused on these cells to determine how a high-fat diet shapes their function and contributes to lung inflammation.
In their experiments, mice were fed either a standard chow or a high-fat diet for 12 weeks, which yielded several key findings:
Mice on the high-fat diet developed more pronounced airway inflammation compared with the control group.
Lung macrophages and monocytes accumulated saturated long-chain fatty acids, particularly stearic acid.
This accumulation triggered activation of the NLRP3 inflammasome and caused neutrophil-dominant lung inflammation even without additional irritants.
Exposure to a model of airway inflammation further amplified disease severity in the high-fat diet group.
Stearic acid specifically intensified inflammasome activation and lung inflammation, while diets enriched with oleic acid reduced inflammatory signals and eased airway irritation.
Blocking interleukin-1β (IL-1β) or inhibiting the endonuclease IRE1α protected mice from stearic acid–induced lung damage, indicating possible therapeutic targets.
Human analysis revealed that bronchoalveolar lavage fluid from individuals with obesity-associated asthma contained lung monocytes with an inflammatory profile similar to that of those in high-fat–fed mice.
These findings suggest that long-chain saturated fatty acids can drive asthma-like inflammation in humans, mirroring the mechanisms observed in animals.
These results build on earlier evidence linking high-fat diets to airway problems but go a step further by identifying a specific dietary trigger and immune pathway. According to McCright and colleagues, the work highlights that nutrition influences more than just weight and metabolic health—it can directly prime immune cells in the lungs, shaping inflammatory responses.
“By pinpointing stearic acid as a driver of lung immune activation, the study raises the possibility that reducing certain saturated fats or countering their effects pharmacologically could help manage or prevent asthma, especially in people with obesity-related respiratory conditions,” the authors concluded.
Reference:
McCright, S. J., Harding, O., Chini, J., DeMarco, N., Hung, Y., Pastore, C. F., Lu, W., Rabinowitz, J., Henao-Mejia, J., Herbert, B. R., Young, L. R., & Hill, D. A. (2025). Dietary saturated fatty acids promote lung myeloid cell inflammasome activation and IL-1β–mediated inflammation in mice and humans. Science Translational Medicine. https://doi.org/adp5653
