Obesity increases airway hyperresponsiveness via the TNF-α pathway and treating obesity induces recovery.
Obesity increases airway hyperresponsiveness via the TNF-α pathway and treating obesity induces recovery.
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DOI：
10.1371/journal.pone.0116540
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Park JW
中科院分区：
文献类型：
--
作者：
Kim JY;Sohn JH;Lee JH;Park JW
肥胖是过敏性哮喘的已知危险因素。它被认为是通过巨噬细胞激活导致多种炎症性疾病发病机制的关键参与者，这对于过敏性哮喘的发展也至关重要。我们研究了肥胖相关哮喘的机制，以及在肥胖相关哮喘模型中通过运动或饮食治疗肥胖是否可以改善哮喘的严重程度。我们通过高脂肪喂养和卵清蛋白诱导哮喘（lean-OVA 或 DIO-OVA）在 C57BL/6 小鼠中产生饮食诱导肥胖 (DIO)。然后用肿瘤坏死因子 (TNF)-α 中和抗体作为 TNF-α 阻断剂或含 Cl2MDP 的脂质体治疗 DIO-OVA 小鼠，以诱导肺泡巨噬细胞缺陷。为了治疗肥胖，DIO-OVA 小鼠受到饮食限制或锻炼。分析病理生理学和免疫学反应。与瘦 OVA 小鼠相比，DIO-OVA 小鼠的气道高反应性 (AHR)、肺组织中的血清 IgE 和 TNF-α 水平有所增加。与 DIO-OVA 小鼠相比，DIO-OVA 小鼠中 TNF-α 阻断和肺泡巨噬细胞消耗均降低了 AHR。通过运动或饮食方式治疗肥胖症也降低了 DIO-OVA 小鼠的肺部 TNF-α 水平和 AHR。这些结果表明，恢复正常体重是降低 TNF-α 水平的适当策略，控制炎症可能有助于改善哮喘严重程度和控制肥胖相关哮喘。
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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影响因子：
4.9
作者：
Feola, David J.;Garvy, Beth A.;Murphy, Brian S.
通讯作者：
Murphy, Brian S.
影响因子：
24.3
作者：
Rönmark, E;Andersson, C;Lundbäck, B
通讯作者：
Lundbäck, B
影响因子：
6.1
作者：
Scott, H. A.;Gibson, P. G.;Wood, L. G.
通讯作者：
Wood, L. G.
影响因子：
8.3
作者：
Gibson, Peter G
通讯作者：
Gibson, Peter G
DOI：
10.1164/rccm.201203-0573oc
发表时间：
2012-10-01
影响因子：
24.7
作者：
Sideleva, Olga;Suratt, Benjamin T.;Dixon, Anne E.
通讯作者：
Dixon, Anne E.