Saturated Fatty Acid Increases Lung Macrophages and Augments House Dust Mite-Induced Airway Inflammation in Mice Fed with High-Fat Diet

Abstract

Obesity is one of the phenotypes of severe asthma, which is considered to be a heterogeneous syndrome; however, its interaction with airway inflammation is not fully understood. The aim of this study was to clarify the role of saturated fatty acids in augmenting airway inflammation induced by house dust mite (HDM) in obesity. Subjects were Balb/c mice fed a high-fat diet (HFD) for 10 weeks, followed by sensitization and exposure to HDM. Subjects were also administered palmitic acid (PA) for 4 weeks with concurrent sensitization and exposure to HDM. Airway inflammation was assessed by quantifying the amount of inflammatory cells in bronchoalveolar lavage (BAL) and airway resistance was measured. In vitro, lipopolysaccharide (LPS)-primed macrophages were stimulated by PA. The amount of monocyte chemoattractant protein-1 (MCP-1), interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α) was examined in the supernatant. Compared to normal chow mice, HFD mice underwent significant increases in body weight; increases in number of lung macrophages, including circulating monocytes and alveolar macrophages; and increases in bronchoalveolar lavage fluid (BALF) total cell count, including neutrophils but not eosinophils, after HDM sensitization and exposure. In vitro, PA induced MCP-1 and augmented LPS-primed production of IL-1β and TNF-α in macrophages. Among HDM mice that were administered PA, there was an increase BALF total cell count, including neutrophils but not eosinophils, compared to vehicle mice. In conclusion, saturated fatty acid increased the number of lung macrophages and augmented HDM-induced neutrophilic airway inflammation in a HFD mouse model.

The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model

“…IL-33 from monocytes recruited to the lung contributes to the pathogenesis of HDM-induced airway inflammation [12]. Saturated fatty acids increase the recruitment of lung macrophages and augments HDM-induced airway inflammation in obese mice [47]. In the present study, the number of interstitial macrophages (defined as CD45 + , CD11c low , CD11b + , and Ly6c − cells) was significantly decreased with EM900 or CAM treatment in HDM and poly(I:C)-induced airway inflammation in mice.…”

Obesity and severe asthma

“…These authors and others (50) also reported greater sputum IL-17A, a cytokine important for neutrophil recruitment, in the obese than the lean patients suggesting that this cytokine may be contributing the neutrophil recruitment in these patients. Data from animal models also suggest a link between IL-17A and obese asthma (51). Obese mice typically exhibit innate airway hyperresponsiveness, but this hyperresponsiveness is not observed if the animals are IL-17A deficient (52).…”

The impact of nutrition on COVID-19 susceptibility and long-term consequences

“…This triggers activation of canonical inflammatory signaling pathways that produce proinflammatory mediators and other effectors of the innate immune system (Rogero and Calder, 2018). Furthermore, consumption of a HFD in mice increased macrophage infiltration to lung tissue, specifically in the alveoli (Tashiro et al, 2017). This is especially relevant to COVID-19 patients given the high rate of infection among lung alveolar epithelial cells and the involvement of lung tissue inflammation and alveolar damage in COVID-19 pathology (Xu et al, 2020).…”