Obesity-Associated Metabolomic and Functional Reprogramming in Neutrophils from Horses with Asthma

Equine asthma is a chronic respiratory disease characterised by neutrophilic inflammation, airway hyperresponsiveness, and impaired pulmonary function. Obesity, increasingly prevalent among domestic horses, has been identified as a potential risk factor for exacerbating inflammatory conditions. This study aimed to explore whether obesity modifies neutrophil metabolism and inflammatory responses in horses affected by asthma. Six asthmatic horses in clinical remission were categorised into two groups: obese and non-obese, based on body condition score. Serum levels of interleukin-1β (IL-1β) and peripheral blood neutrophil counts were significantly higher in obese horses, indicating a heightened systemic inflammatory state. Neutrophils from obese horses displayed a stronger oxidative burst following zymosan stimulation and elevated IL-1β gene expression in response to lipopolysaccharide, suggesting a hyperinflammatory phenotype. Metabolomic profiling of neutrophils identified 139 metabolites, with notable differences in fatty acids, branched-chain amino acids, and tricarboxylic acid (TCA) cycle intermediates. Pathway enrichment analysis revealed significant alterations in fatty acid biosynthesis, amino acid metabolism, and glutathione-related pathways. Elevated levels of itaconate, citraconic acid, and citrate in obese horses indicate profound metabolic reprogramming within neutrophils. These results suggest that obesity promotes a distinct neutrophil phenotype marked by increased metabolic activity and heightened responsiveness to inflammatory stimuli. This altered profile may contribute to the persistence or worsening of airway inflammation in asthmatic horses. The findings underscore the importance of addressing obesity in the clinical management of equine asthma and open avenues for further research into metabolic-targeted therapies in veterinary medicine.