People with obesity can experience obesity-associated asthma. Unlike asthma induced by allergens, obesity-associated asthma is characterized by inflammatory macrophages and monocytes and high levels of neutrophils in the lungs.1 The mechanisms underlying this immune cell activation in the lung and its contribution to obesity-associated asthma have not been well characterized.
A team led by David Hill, an immunologist at the University of Pennsylvania, sought to investigate this question further. “Prior to this study, many suspected that childhood obesity was causing this form of asthma. However, we were observing neutrophilic asthma in children who weren’t obese, which is why we suspected there might be another mechanism,” he said in a press release.
His team showed that specific lipids in a high-fat diet activated resident immune cells in the lungs of mice. These activated macrophages and monocytes led to an elevated inflammatory response in an asthma model.2 The findings, published in Science Translational Medicine, offer a path to new treatment options for people with obesity-associated asthma.
The researchers saw that feeding mice a high-fat diet for 12 weeks increased the population of inflammatory macrophages and monocytes in their lungs. These cells also had increased intracellular lipid accumulation, where the team observed an increased amount of saturated long-chain fatty acid. When they treated these cells or bone marrow derived macrophages with one of the highly abundant saturated fatty acids, stearic acid, they saw that this activated a key inflammatory complex, the inflammasome.
To confirm that these effects were independent of other obesity-related changes, the team fed a new set of mice a high-fat diet where the lipid component is predominantly stearic acid. After four weeks, the researchers showed that the diet activated macrophages and monocytes in the lungs similarly to the full high-fat diet.
Next, the team developed an asthma model that replicated the inflammation seen in obesity-associated asthma by treating mice with a mixture of house dust mite extracts and lipopolysaccharide. Compared to mice fed a normal diet, those fed a diet with increased stearic acid experienced worsened airway inflammation and pulmonary function. The team showed that the activation of the inflammasome in lung resident monocytes and macrophages caused this aggravated immune response.
Finally, the researchers studied lung fluid from people with varying body mass indexes (BMIs). They saw that individuals with higher BMIs had more inflammatory monocytes with greater lipid content and evidence of inflammasome activation, and they saw that this further increased in people with asthma.
“While there are many risk factors and triggers that are associated with asthma, this study provides evidence about how specific dietary components are linked to a particularly difficult-to-treat form of asthma. These findings are encouraging because they provide new treatment strategies and suggest that targeted dietary modifications may help prevent this asthma type,” said Lisa Young, a physician scientist at the University of Pennsylvania and study coauthor.
- Scott HA, et al. Airway inflammation is augmented by obesity and fatty acids in asthma. Eur Resp J. 2011;38(3):594-602.
- 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.
