High fat diet induces airway hyperresponsiveness in mice

Fricke, Kathrin; Vieira, Marcela; Younas, Haris; Shin, Mi Kyung; Bevans‐Fonti, Shannon; Berger, Slava; Lee, Rachel; D’Alessio, Franco R.; Zhong, Qian; Nelson, Andrew; Loube, Jeffrey; Sanchez, Ian; Hansel, Nadia N.; Mitzner, Wayne; Polotsky, Vsevolod Y.

doi:10.1038/s41598-018-24759-4

Cited by 29 publications

(29 citation statements)

References 23 publications

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“…Finally, our work establishes that allergic airway inflammation in obesity leads to alterations in the BM compartment and potentiate generation of proinflammatory lung DCs. In consistent with others, we found that HFD exacerbates airway inflammation, as indicated by an increase in BAL cellularity, plasma IgE, and IgG1 levels, and Th2/Th1 immune response (19,53,54). We show lung CD11b + conventional DCs, which are specialized for antigen presentation and to generate T cell-mediated immune responses in allergic asthma (55)(56)(57), notably increased by HDM sensitization.…”

Section: Discussionsupporting

confidence: 91%

Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway

et al. 2020

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Proliferation of dendritic cell (DC)-restricted progenitor cells in bone marrow compartment is tightly regulated at steady state and responds to multiple tissue-specific triggers during disturbed homeostasis such as obesity. DCs in the lung stem from a rapidly dividing DC-restricted progenitor cells and are effective at generating adaptive immune responses in allergic airway inflammation. Precisely, how DC-restricted progenitor expansion and differentiation are influenced by airway inflammation to maintain constant supply of myeloid DCs is poorly understood. Here we show that a high fat diet (HFD) induces oxidative stress and accelerates the expansion of DC-restricted progenitor cells in bone marrow and correlates with persistent induction of p38 mitogen activated protein kinase (MAPK), which is blocked with a selective p38α/β MAPK inhibitor. Mice fed a HFD and sensitized to inhaled allergen house dust mite (HDM) led to alterations of DC-restricted progenitor cells that were characterized by increased expansion and seeding of lung DCs in airway inflammation. Mechanistically, we establish that the expansion induced by HFD dysregulates the expression of a disintegrin and metallopeptidase domain 17 (Adam17) and is required for p38 MAPK activation in DC-restricted progenitors. These results demonstrates that obesity produces persistent changes in DC precursors and that elevation of Adam17 expression is tightly coupled to p38 MAPK and is a key driver of proliferation. Altogether, these data provide phenotypic and mechanistic insight into dendritic cell supply chain in obesity-associated airway inflammation.

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Section: Discussionsupporting

confidence: 91%

Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway

et al. 2020

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“…Previous studies generally focused on the airway responsiveness in obesity associated with asthma independent of sex. 30 Our results showed that a high-fat diet in female OVA-sensitized rats was very susceptible to AHR compared with male rats. Indeed, it is clear from the results that obesity in OVA-sensitized condition has the most impact on the tracheal responsiveness of females.…”

Section: Discussionmentioning

confidence: 55%

Effect of High-fat Diet on Tracheal Responsiveness to Methacholine and Insulin Resistance Index in Ovalbumin-sensitized Male and Female Rats

Ghobadi

Alipour

Keyhanmanesh

et al. 2019

IJAAI

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Epidemiological and clinical studies have demonstrated a close association between obesity and asthma. The current study investigated the effect of high-fat diet on tracheal responsiveness to methacholine and insulin resistance in ovalbumin (OVA) sensitized male and female rats. The rats were divided into eight groups (n=6 per group): female with the normal diet (F+ND), male with the normal diet (M+ND), female OVA-sensitized with the normal diet (F+SND), male OVA-sensitized with the normal diet (M+SND), female with high-fat diet (F+HFD), male with high-fat diet (M+HFD), female OVA-sensitized with high-fat diet (F+SHFD), and male OVA-sensitized with high-fat diet (M+SHFD). All rats were fed for 8 weeks with high-fat diet or standard pelts, and for another 4 weeks, they were sensitized with OVA or saline. At the end of the study, the tracheal responsiveness to methacholine, serum insulin, and blood glucose levels was measured. Also, insulin resistance indexes were determined. OVA-sensitization and diet-induced obesity caused the curve of methacholine concentration response to shifting to the left. In addition, results indicated that the EC50 (the effective concentration of methacholine generating 50% of peak response) in F+SHFD rats was statistically lower than M+SHFD group (p<0.05). Moreover, insulin resistance was higher in the F+SHFD than the M+SHFD group (p<0.001). These results suggest that insulin resistance and metabolic syndrome may be involved in the pathogenesis of obesity associated with OVA-sensitized rats condition, especially in female animals.

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“…Previous studies suggest that obesity serves as a risk factor for the development, severity and weaker responsiveness to standard asthma medication . In the late‐onset non‐allergic phenotype of obesity‐associated asthma (LONA), airway hyperresponsiveness (AHR) is considered a consequence of lung compression and structural lung modifications due to increased body weight . Furthermore, animal models show that LONA is associated with T helper (Th)1‐ and Th17 aberrant immune responses .…”

Section: Introductionmentioning

confidence: 99%

“…3 In the late-onset non-allergic phenotype of obesity-associated asthma (LONA), airway hyperresponsiveness (AHR) is considered a consequence of lung compression and structural lung modifications due to increased body weight. 4,5 Furthermore, animal models show that LONA is associated with T helper (Th)1-and Th17 aberrant immune responses. 6,7 However, next to LONA, an early-onset allergic form of obesity-associated asthma has been described (EOA), 8 which is characterized by a more classical allergen-driven eosinophilia and Th2 differentiation without body weight-induced modulations.…”

Section: Introductionmentioning

confidence: 99%

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Schröder

Wiese

Ender

et al. 2019

Clin Experimental Allergy

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Background A close association between obesity and asthma has been described. The nature of this association remains elusive, especially with respect to allergic asthma. Controversial findings exist regarding the impact of short‐term high‐fat diet (HFD) feeding on the development of allergic asthma. Objective To delineate the impact of short‐term HFD feeding on the development of experimental allergic asthma. Methods Female C57BL/6JRJ mice were fed with a short‐term HFD or chow diet (CD) for 12 weeks. Allergic asthma was induced by intraperitoneal OVA/alum sensitization followed by repeated OVA airway challenges. We determined airway hyperresponsiveness (AHR) and pulmonary inflammation by histologic and flow cytometric analysis of immune cells. Furthermore, we assessed the impact of HFD on dendritic cell (DC)‐mediated activation of T cells. Results Female mice showed a mild increase in body weight accompanied by mild metabolic alterations. Upon OVA challenge, CD‐fed mice developed strong AHR and airway inflammation, which were markedly reduced in HFD‐fed mice. Mucus production was similar in both treatment groups. OVA‐induced increases in DC and CD4+ T‐cell recruitment to the lungs were significantly attenuated in HFD‐fed mice. MHC‐II expression and CD40 expression in pulmonary CD11b+ DCs were markedly lower in HFD‐fed compared to CD‐fed mice, which was associated in vivo with a decreased T helper (Th) 1/17 differentiation and Treg formation without impacting Th2 differentiation. Conclusions/clinical relevance These findings suggest that short‐term HFD feeding attenuates the development of AHR, airway inflammation, pulmonary DC recruitment and MHC‐II/CD40 expression leading to diminished Th1/17 but unchanged Th2 differentiation. Thus, short‐term HFD feeding and associated metabolic alterations may have protective effects in allergic asthma development.

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High fat diet induces airway hyperresponsiveness in mice

Cited by 29 publications

References 23 publications

Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway

Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway

Effect of High-fat Diet on Tracheal Responsiveness to Methacholine and Insulin Resistance Index in Ovalbumin-sensitized Male and Female Rats

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

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