Translational and clinical immunologySaturated fatty acids, obesity, and the nucleotide oligomerization domain–like receptor protein 3 (NLRP3) inflammasome in asthmatic patients
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Section snippets
Study 1: Obese versus nonobese asthmatic patients—Cross-sectional comparison of inflammatory pathways
A cross-sectional observational study was conducted in 127 adult asthmatic patients categorized as nonobese (body mass index [BMI], <30 kg/m2; n = 51) or obese (BMI, ≥30 kg/m2; n = 76). Data from a subset of these subjects have been reported previously.14, 15, 16 Subjects fasted overnight, and asthma medications were withheld (short-acting bronchodilators, 6 hours; long-acting bronchodilators and inhaled corticosteroids, 24 hours). Blood was collected, and spirometry and sputum induction were
Obese versus nonobese asthmatic patients: Cross-sectional comparison of inflammatory pathways
Subjects' characteristics are described in Table II. Obese asthmatic patients had higher plasma levels of total FAs, SFAs, monounsaturated FAs, C16:0, C18:0, and C20:4n-6 compared with nonobese asthmatic patients. Nanostring analysis of sputum cell gene expression in obese versus nonobese asthmatic patients identified 13 genes with a fold change of greater than 1.5 that were expressed differentially (Table III). The most significantly upregulated gene in obese asthmatic patients was IL5,
Discussion
This study provides important new insight into airway NLRP3 inflammasome activity in asthmatic patients with a high BMI and after excess macronutrient intake. We have shown increased circulating FA levels, activation of the innate immune receptor NOD1, and increased NLRP3 activity and IL-1β protein levels in obese asthmatic patients. We have also determined that SFAs induce postprandial airway inflammation with increased TLR4, NLRP3, and IL-1 pathway gene expression in nonobese
References (47)
- et al.
Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013
Lancet
(2014) - et al.
Effects of weight loss on peak flow variability, airways obstruction, and lung volumes in obese patients with asthma
Chest
(2000) - et al.
Influence of obesity on response to fluticasone with or without salmeterol in moderate asthma
Respir Med
(2007) - et al.
A high-fat challenge increases airway inflammation and impairs bronchodilator recovery in asthma
J Allergy Clin Immunol
(2011) - et al.
Manipulating antioxidant intake in asthma: a randomized controlled trial
Am J Clin Nutr
(2012) - et al.
Heterogeneity of airway inflammation in persistent asthma—evidence of neutrophilic inflammation and increased sputum interleukin-8
Chest
(2001) - et al.
Improved antioxidant and fatty acid status of patients with cystic fibrosis after antioxidant supplementation is linked to improved lung function
Am J Clin Nutr
(2003) - et al.
Inflammation and lipid signaling in the etiology of insulin resistance
Cell Metab
(2012) - et al.
Current role of the NLRP3 inflammasome on obesity and insulin resistance: a systematic review
Metabolism
(2017) - et al.
Body mass index correlates with pollutant-induced interleukin-1beta in sputum and blood
Ann Allergy Asthma Immunol
(2015)
Postprandial recruitment of neutrophils may contribute to endothelial dysfunction
J Lipid Res
Effects of rosuvastatin on postprandial leukocytes in mildly hyperlipidemic patients with premature coronary sclerosis
Atherosclerosis
In vivo regulation of plasma free fatty acids in insulin resistance
Metabolism
Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program
Am J Respir Crit Care Med
Obesity is a risk factor for dyspnea but not for airflow obstruction
Arch Intern Med
Influence of body mass index on the response to asthma controller agents
Eur Respir J
Mechanisms and treatments for severe, steroid-resistant allergic airway disease and asthma
Immunol Rev
Inflammasomes in respiratory diseases
Thorax
Airway inflammation is augmented by obesity and fatty acids in asthma
Eur Respir J
Obesity in asthma: more neutrophilic inflammation as a possible explanation for a reduced treatment response
Allergy
Obese individuals with asthma preferentially have a high IL-5/IL-17A/IL-25 sputum inflammatory pattern
Am J Respir Crit Care Med
Nutrient sensing and inflammation in metabolic diseases
Nat Rev Immunol
Cited by (0)
The project was funded by the National Health and Medical Research Council (NHMRC) of Australia. P.G.G. is supported by an NHMRC Practitioner Fellowship, and P.M.H. is supported by an NHMRC Principal Research Fellowship and a Brawn Fellowship, Faculty of Health and Medicine, University of Newcastle.
Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.