A NEW study shows that diets rich in saturated long-chain fatty acids can reprogramme lung macrophages, driving inflammation at baseline and worsening airway disease, with findings conserved between mice and humans with obesity-associated asthma.
Resident tissue macrophages (RTM) are central to lung immune regulation, yet the influence of dietary components on their function is poorly understood. Researchers investigated how high-fat (HF) diets affect RTM phenotype and inflammatory responses. Mice were fed diets enriched with either stearic acid (a saturated long-chain fatty acid) or oleic acid (its monounsaturated counterpart). Lung tissue was analysed for lipid accumulation, inflammasome activation, and inflammatory cell infiltration. Parallel studies examined bronchoalveolar lavage fluid from humans with obesity-associated asthma.
Mice on an HF diet accumulated stearic acid in RTMs, showing priming and activation of the NLRP3 inflammasome. Increased dietary stearic acid was sufficient to cause neutrophil-predominant lung inflammation at steady state and to exacerbate a model of airway inflammation. By contrast, dietary oleic acid reduced inflammasome activation and attenuated airway inflammation. Mechanistically, depletion of IL-1β or pharmacological inhibition of IRE1α protected against stearic acid-induced lung inflammation. In humans, a population of lung monocytes with features of HF diet-induced RTM activation was identified in bronchoalveolar lavage samples from obese patients with asthma, supporting translational relevance.
These findings provide evidence that long-chain fatty acids can directly regulate lung immune tone and exacerbate airway disease. Targeting lipid-driven immune pathways may represent a therapeutic strategy in obesity-related asthma.
Reference
McCright SJ et al. Dietary saturated fatty acids promote lung myeloid cell inflammasome activation and IL-1β-mediated inflammation in mice and humans. Sci Transl Med. 2025;17(813):eadp5653.
