Saturated fatty acids, obesity and the NLRP3 inflammasome in asthma

Publication date: Available online 30 May 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Lisa G. Wood, Qian Li, Hayley A. Scott, Sandra Rutting, Bronwyn S. Berthon, Peter G. Gibson, Phil M. Hansbro, Evan Williams, Jay Horvat, Jodie L. Simpson, Paul Young, Brian G. Oliver, Katherine J. Baines
BackgroundBoth obesity and high dietary fat intake activate the NLRP3 inflammasome.ObjectiveWe aimed to examine NLRP3 inflammasome activity in the airways of obese asthmatics, following macronutrient overload and in immune cells challenged by inflammasome triggers.MethodsStudy 1: Cross-sectional, observational study of non-obese (n=51) and obese (n=76) asthmatic adults. Study 2: Randomized, crossover, acute feeding study in 23 asthmatic adults (n=12 non-obese, n=11 obese). Subjects consumed 3 isocaloric meals on 3 separate occasions: saturated fatty acid (SFA), n-6 polyunsaturated (PUFA) and carbohydrate (CHO); and were assessed at 0 and 4 hours. For Study 1 and 2, airway inflammation was measured using sputum differential cell counts, IL-1β protein (ELISA) and sputum cell gene expression (Nanostring nCounter). Study 3: Peripheral blood neutrophils and monocytes were isolated using Ficoll density gradient and magnetic bead separation, and incubated with or without palmitic acid, LPS or TNFα for 24 hours and IL-1β release measured (ELISA).ResultsStudy 1: NLRP3 and NOD1 gene expression were upregulated, and sputum IL-1β protein levels higher, in obese versus non-obese asthmatics. Study 2: The SFA meal led to increases in sputum %neutrophils and sputum cell gene expression of TLR4 and NLRP3 at 4 hours, in non-obese asthmatics. Study 3: Neutrophils and monocytes released IL-1β when challenged with a combination of palmitic acid and LPS or TNFα.ConclusionThe NLRP3 inflammasome is a potential therapeutic target in asthma. Behavioural interventions that reduce fatty acid exposure, such as weight loss and dietary saturated fat restriction warrant further exploration.Clinical implicationsBoth obesity and saturated fat intake cause NLRP3 inflammasome-mediated airway inflammation in asthma. Hence weight loss and dietary fat restriction warrant further exploration as anti-inflammatory strategies in asthma.

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Teaser

The NLRP3 inflammasome is upregulated in obese asthmatics and following a high saturated fat meal in non-obese asthmatics. Both reversal of obesity and restriction of dietary saturated fat intake warrant further exploration as anti-inflammatory strategies in asthma.


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