Dissociation between lung inflammation and hyperresponsiveness in a murine model of obesity

<bold>Introduction:</bold> Obesity is a risk factor in asthma, some reports have shown that nearly 75 percent of emergency room visits for asthma have been among obese individuals, and several cross-sectional studies have found an increase in the prevalence of asthma among obese patients. In this study we compared lung inflammation and hyperresponsiveness induced by HDM in males high fat diet (HFD) and standard chow (SC) fed mice. <bold>Methods:</bold> C57/BL6 male mice were fed a 60% HFD or SC for 13 weeks. On week 10, they were sensitized to HDM (60 mg/i.n), once a week for 3 weeks. Forty-eight hours after last challenge, all animals were euthanised and lung lavage or lung mechanics performed (Flexivent System). <bold>Results:</bold> Sensitization to HDM induced an increase in the total number of leukocytes as well as eosinophils in bronchoalveolar lavage that was not different between HFD and SC mice (total cells: HFD Sham 15+1, HFD HDM 112+30; SC Sham: 14.6+2, SC HDM 87+20. Eos: HFD Sham 0+0, HFD HDM 36+11; SC Sham: 0+0, SC HDM 39+13 x 10<sup>4</sup>/mL, N=11-13, respectively). Airways resistance peak response to 24mg/mL of methacholine induced a significant increase in HDM SC mice but not in HFD mice (Rn HFD Sham: 2.5+0.6, HFD HDM: 2.5+0.9; SC sham:1.2+0.1, SC HDM: 3.12+1.2* cmH<sub>2</sub>O.s/mL, N=6/group, *p<0.05). <bold>Conclusion:</bold> Our data suggest that HDM increases leukocyte numbers in the lung of HFD mice however, it does not affect hyperresponsiveness, which is already increased in HFD sham mice in comparison to SC animals.

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Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.pa4827
Primary Topic
Cardiovascular Disease and Adiposity
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article
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article

Dissociation between lung inflammation and hyperresponsiveness in a murine model of obesity

Amanda Virginia Cavalcante, Simon C. Pitchford, Yanira Riffo‐Vasquez, Alcibey Alvarado
Cardiovascular Disease and Adiposity
article

Dissociation between lung inflammation and hyperresponsiveness in a murine model of obesity

Amanda Virginia Cavalcante, Simon C. Pitchford, Yanira Riffo‐Vasquez, Alcibey Alvarado
article en

Abstract

<bold>Introduction:</bold> Obesity is a risk factor in asthma, some reports have shown that nearly 75 percent of emergency room visits for asthma have been among obese individuals, and several cross-sectional studies have found an increase in the prevalence of asthma among obese patients. In this study we compared lung inflammation and hyperresponsiveness induced by HDM in males high fat diet (HFD) and standard chow (SC) fed mice. <bold>Methods:</bold> C57/BL6 male mice were fed a 60% HFD or SC for 13 weeks. On week 10, they were sensitized to HDM (60 mg/i.n), once a week for 3 weeks. Forty-eight hours after last challenge, all animals were euthanised and lung lavage or lung mechanics performed (Flexivent System). <bold>Results:</bold> Sensitization to HDM induced an increase in the total number of leukocytes as well as eosinophils in bronchoalveolar lavage that was not different between HFD and SC mice (total cells: HFD Sham 15+1, HFD HDM 112+30; SC Sham: 14.6+2, SC HDM 87+20. Eos: HFD Sham 0+0, HFD HDM 36+11; SC Sham: 0+0, SC HDM 39+13 x 10<sup>4</sup>/mL, N=11-13, respectively). Airways resistance peak response to 24mg/mL of methacholine induced a significant increase in HDM SC mice but not in HFD mice (Rn HFD Sham: 2.5+0.6, HFD HDM: 2.5+0.9; SC sham:1.2+0.1, SC HDM: 3.12+1.2* cmH<sub>2</sub>O.s/mL, N=6/group, *p<0.05). <bold>Conclusion:</bold> Our data suggest that HDM increases leukocyte numbers in the lung of HFD mice however, it does not affect hyperresponsiveness, which is already increased in HFD sham mice in comparison to SC animals.

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