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

Joo Young Kim,Jae-Hyun Lee,Jung-Ho Sohn,Jung-Won Park,Christian Taube

doi:10.1371/journal.pone.0116540

Joo Young Kim, Jae-Hyun Lee + Show 3 more

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https://doi.org/10.1371/journal.pone.0116540

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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.

Highlights

Obesity is a metabolic disease and a major risk factor for several noncommunicable diseases, such as diabetes, and cardiovascular diseases
The diet-induced obesity (DIO) mice were fed a high fat diet (HFD) and their body weights significantly increased by 75% more than the lean mice at 16 weeks (Fig. 1A-B)
As a representative pathologic change in the lung of the asthma model, goblet cell hyperplasia in the peri-bronchiolar area was measured, but we found no significant differences between the lean-OVA and DIO-OVA mice (S1 Fig.)

Summary

Introduction

Obesity is a metabolic disease and a major risk factor for several noncommunicable diseases, such as diabetes, and cardiovascular diseases. The World Health Organization estimates that more than 1.4 billion adults are overweight, and of these overweight adults, over 200 million men and nearly 300 million women are obese [1]. Obesity is associated with a later onset of asthma in the development, control and severity [2]. Several studies have focused on the heterogeneity of asthma phenotypes based on clinical characteristics, triggers, or general inflammatory processes, even though asthma has been considered a single disease for years [3].

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