Background/Aims: A high fat meal is associated with airway inflammation in asthma, but the mechanisms are not well understood. This aim of this study was to use microarray techniques to examine the molecular mechanisms of fat-induced airway inflammation in asthma compared with healthy controls.
Methods: Subjects with asthma (n=11) and healthy controls (n=8) were provided with a high-fat, high energy meal, containing total energy (TE) of 3846 kJ and 48g (49% of TE) total fat, including 20.5 g (21% of TE) saturated fat. Sputum was induced at 0 and 4 hours and gene expression was examined by microarray and quantitative real-time PCR(qPCR).
Results: Following the high fat dietary challenge, 168 entities were significantly differentially expressed greater than 1.5 fold in subjects with asthma. Five genes involved in immune system processes were selected for qPCR analysis (S100P, S100A16, MAL, MUC1 and NLPR12). qPCR confirmed that S100P, S100A16, MAL and MUC1 were significantly increased in the asthma group post-meal. There was a moderate and significant correlation between the change in S100P and MUC1 gene expression and the change in sputum %neutrophils following the high fat meal (r=0.552, p=0.024; r=0.495, p=0.045respectively). NLRP12 gene expression at 4 hours strongly correlated with the change in total and saturated non-esterified plasma fatty acid levels at 2 hours(r=0.555, p=0.028; r=0.53, p=0.037respectively).
Conclusions: Our data identifies several genes that contribute to neutrophilic airway inflammation following consumption of a high fat meal in asthmatics, which may prove to be therapeutic targets for immunomodulation.Funding Sources: NHMRC, HMRI and TSANZ