A new diagnostic tool and treatment target may be on the horizon, thanks to the discovery of a critical genetic link between obesity and asthma.
In their paper, “Identification and Validation of ALOX15 as a Robust Diagnostic Biomarker for Obesity-Associated Asthma: An Integrative Bioinformatic and Experimental Study,” scientists identified a gene known as ALOX15 as a central driver in obesity-associated asthma, a more severe and treatment-resistant form of the disease. Their findings were published in the Journal of Inflammation Research.
The paper’s authors noted that treating asthma among rising obesity cases continues to be a global burden, as excess weight makes the condition more difficult to control. However, they said, the biological mechanisms behind asthma and obesity have remained unclear.
Their research addresses this gap, revealing how metabolic dysfunction caused by high-fat diets may directly trigger inflammatory pathways in the lungs. Using an innovative approach, the research team combined large genetic datasets with advanced machine learning models to identify genes involved in both obesity and asthma.
From an initial pool of hundreds of genes, the analysis narrowed the list to four key candidates: ALOX15, IL1R1, TNFAIP3 and NLRP3.
ALOX15 emerged as the strongest predictor, consistently demonstrating high diagnostic performance across multiple datasets. The gene’s predictive power was particularly notable, achieving strong accuracy scores (AUC greater than 0.7) and ranking as the most influential variable in machine learning models that assessed asthma risk.
To validate the computational findings, researchers conducted experiments on mouse models consuming a high-fat diet. The results were striking:
- Mice on high-fat diets showed greater lung inflammation and airway damage.
- ALOX15 expression was significantly higher in these mice compared to those on normal diets.
- Asthma symptoms were more severe when obesity was present.
According to researchers, these findings suggest that ALOX15 plays a direct role in worsening asthma under obese conditions, rather than being a coincidental marker. They noted that ALOX15 is involved in the metabolism of fatty acids, particularly arachidonic acid, which produces molecules known to regulate inflammation.
The study found that higher levels of ALOX15 were linked to:
- Increased eosinophils, a key immune cell in allergic inflammation
- Activation of major inflammatory pathways, including NF-κB signaling
- Enhanced airway remodeling and mucus production
The gene appears to act as a bridge between metabolic stress (from obesity) and immune system overreaction in the lungs, scientists said.
Because of its strong and consistent performance across datasets and experimental models, the study’s authors noted ALOX15 could serve as:
- A diagnostic biomarker to identify high-risk asthma patients
- A target for new therapies aimed at reducing inflammation in obese individuals
This is especially important for patients with obesity-associated asthma, who often respond poorly to standard treatments.
Although the findings are promising, researchers cautioned that more work is needed to confirm ALOX15’s role in human patients and to develop targeted treatments. Their study relied partly on public datasets and animal models, which may not fully capture the complexity of human disease, they said.
They indicated the need for future research to:
- Test ALOX15 in larger human populations
- Explore drugs that can block or regulate its activity
- Understand how it interacts with other immune and metabolic pathways
By uncovering the role of ALOX15, the authors said they believe their research brings the medical community one step closer to developing personalized treatments that account for a patient’s metabolic profile — potentially improving outcomes for millions living with both obesity and asthma.
