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Obesity increases airway hyperresponsiveness via the TNF-α pathway and treating obesity induces recovery

 Joo Young Kim  ;  Jung-Ho Sohn  ;  Jae-Hyun Lee  ;  Jung-Won Park 
 PLOS ONE, Vol.10(2) : e0116540, 2015 
Journal Title
Issue Date
Animals ; Antibodies, Neutralizing/administration & dosage* ; Antibodies, Neutralizing/adverse effects ; Body Weight/drug effects ; Clodronic Acid/administration & dosage* ; Diet Therapy ; Diet, High-Fat ; Disease Models, Animal ; Exercise Therapy ; Macrophages, Alveolar/drug effects ; Macrophages, Alveolar/pathology ; Mice ; Obesity/complications ; Obesity/etiology ; Obesity/physiopathology ; Obesity/therapy* ; Ovalbumin ; Respiratory Hypersensitivity/chemically induced ; Respiratory Hypersensitivity/drug therapy* ; Respiratory Hypersensitivity/immunology ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Tumor Necrosis Factor-alpha/metabolism
Obesity is a known risk factor for allergic asthma. It has been recognized as a key player in the pathogenesis of several inflammatory disorders via activation of macrophages, which is also vital to the development of allergic asthma. We investigated the mechanism of obesity-related asthma and whether treating obesity through exercise or diet ameliorates the severity of asthma in the obesity-related asthma model. We generated diet-induced obesity (DIO) in C57BL/6 mice by high-fat-feeding and ovalbumin-induced asthma (lean-OVA or DIO-OVA). The DIO-OVA mice were then treated with tumor necrosis factor (TNF)-α neutralizing antibody as a TNF-α blockade or a Cl2MDP-containing liposome to induce an alveolar macrophage deficiency. To treat obesity, the DIO-OVA mice were under dietary restrictions or exercised. The pathophysiological and immunological responses were analyzed. Airway hyperresponsiveness (AHR), serum IgE and TNF-α levels in the lung tissue increased in the DIO-OVA mice compared to the lean-OVA mice. Both the TNF-α blockade and depletion of alveolar macrophages in the DIO-OVA mice decreased AHR compared to the DIO-OVA mice. Treating obesity by exercise or through dietary means also reduced pulmonary TNF-α levels and AHR in the DIO-OVA mice. These results suggest that restoring normal body weight is an appropriate strategy for reducing TNF-α levels, and controlling inflammation may help improve asthma severity and control in obesity-related asthma.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Park, Jung Won(박중원) ORCID logo https://orcid.org/0000-0003-0249-8749
Sohn, Jung Ho(손정호)
Lee, Jae Hyun(이재현) ORCID logo https://orcid.org/0000-0002-0760-0071
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