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Obesity Increases Airway Hyperresponsiveness via the TNF-alpha Pathway and Treating Obesity Induces Recovery

Title
Obesity Increases Airway Hyperresponsiveness via the TNF-alpha Pathway and Treating Obesity Induces Recovery
Authors
Kim, Joo YoungSohn, Jung-HoLee, Jae-HyunPark, Jung-Won
Ewha Authors
김주영
SCOPUS Author ID
김주영scopus
Issue Date
2015
Journal Title
PLOS ONE
ISSN
1932-6203JCR Link
Citation
vol. 10, no. 2
Publisher
PUBLIC LIBRARY SCIENCE
Indexed
SCIE; SCOPUS WOS
Abstract
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 DIOOVA). The DIO-OVA mice were then treated with tumor necrosis factor (TNF)-alpha neutralizing antibody as a TNF-alpha 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-alpha levels in the lung tissue increased in the DIO-OVA mice compared to the lean-OVA mice. Both the TNF-alpha blockade and depletion of alveolar macrophages in the DIO-OVA mice decreased AHR compared to the DIOOVA mice. Treating obesity by exercise or through dietary means also reduced pulmonary TNF-alpha levels and AHR in the DIO-OVA mice. These results suggest that restoring normal body weight is an appropriate strategy for reducing TNF-alpha levels, and controlling inflammation may help improve asthma severity and control in obesity-related asthma.
DOI
10.1371/journal.pone.0116540
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연구기관 > 약학연구소 > Journal papers
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