- Title
- Saturated fatty acids, obesity, and the nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in asthmatic patients
- Creator
- Wood, Lisa G.; Li, Qian; Young, Paul; Oliver, Brian G.; Baines, Katherine J.; Scott, Hayley A.; Rutting, Sandra; Berthon, Bronwyn S.; Gibson, Peter G.; Hansbro, Philip M.; Williams, Evan; Horvat, Jay; Simpson, Jodie L.
- Relation
- National Health and Medical Research Council (NHMRC) of Australia
- Relation
- Journal of Allergy and Clinical Immunology Vol. 143, Issue 1, p. 305-315
- Publisher Link
- http://dx.doi.org/10.1016/j.jaci.2018.04.037
- Publisher
- Mosby
- Resource Type
- journal article
- Date
- 2019
- Description
- Background: Both obesity and high dietary fat intake activate the nucleotide oligomerization domain–like receptor protein 3 (NLRP3) inflammasome. Objective: We aimed to examine NLRP3 inflammasome activity in the airways of obese asthmatic patients after macronutrient overload and in immune cells challenged by inflammasome triggers. Methods: Study 1 was a cross-sectional observational study of nonobese (n = 51) and obese (n = 76) asthmatic adults. Study 2 was a randomized, crossover, acute feeding study in 23 asthmatic adults (n = 12 nonobese and n = 11 obese subjects). Subjects consumed 3 isocaloric meals on 3 separate occasions (ie, saturated fatty acid, n-6 polyunsaturated fatty acid, and carbohydrate) and were assessed at 0 and 4 hours. For Studies 1 and 2, airway inflammation was measured based on sputum differential cell counts, IL-1β protein levels (ELISA), and sputum cell gene expression (Nanostring nCounter). In Study 3 peripheral blood neutrophils and monocytes were isolated by using Ficoll density gradient and magnetic bead separation and incubated with or without palmitic acid, LPS, or TNF-α for 24 hours, and IL-1β release was measured (ELISA). Results: In Study 1 NLRP3 and nucleotide oligomerization domain 1 (NOD1) gene expression was upregulated, and sputum IL-1β protein levels were greater in obese versus nonobese asthmatic patients. In Study 2 the saturated fatty acid meal led to increases in sputum neutrophil percentages and sputum cell gene expression of Toll-like receptor 4 (TLR4) and NLRP3 at 4 hours in nonobese asthmatic patients. In Study 3 neutrophils and monocytes released IL-1β when challenged with a combination of palmitic acid and LPS or TNF-α. Conclusion: The NLRP3 inflammasome is a potential therapeutic target in asthmatic patients. Behavioral interventions that reduce fatty acid exposure, such as weight loss and dietary saturated fat restriction, warrant further exploration.
- Subject
- fatty acids; saturated fat; obesity; inflammasome; airway inflammation; IL-1β; asthma
- Identifier
- http://hdl.handle.net/1959.13/1401561
- Identifier
- uon:34928
- Identifier
- ISSN:0091-6749
- Rights
- © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
- Language
- eng
- Full Text
- Reviewed
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