title: Obesity increases airway hyperresponsiveness via the TNF-α pathway and treating obesity induces recovery.
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 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.
authors: Ewha Womans University College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul, South Korea.
authors: Joo Young
authors: JY
authors: Kim
authors: Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, South Korea.
authors: Jung-Ho
authors: JH
authors: Sohn
authors: Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, South Korea.
authors: Jae-Hyun
authors: JH
authors: Lee
authors: Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, South Korea.
authors: Jung-Won
authors: JW
authors: Park
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage* / Q000009:adverse effects; D001835:Body Weight / Q000187:drug effects; D004002:Clodronic Acid / Q000008:administration & dosage*; D004035:Diet Therapy; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005081:Exercise Therapy; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology; D051379:Mice; D009765:Obesity / Q000150:complications / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D010047:Ovalbumin; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D014409:Tumor Necrosis Factor-alpha; D004002:Clodronic Acid; D010047:Ovalbumin