Mitochondrial Dysfunction Linking Obesity and Asthma

Abstract

The bidirectional epidemiological association between asthma and obesity is well known. Recent evidence suggests that there is an intersection of the pathophysiological molecular pathways leading to either obesity or asthma, at the level of mitochondria. This is not surprising, because mitochondria, beyond their roles as the metabolic powerhouses of the cell, serve as sensors of threats, regulators of stress signaling, and effectors of cytotoxicity. Reduced mitochondrial function and low metabolic activity are well-recognized features of obesity. Three distinct lines of experimental evidences connect mitochondrial dysfunction with asthma. First, asthma is associated with aberrant mitochondrial metabolism. Second, mitochondrial dysfunction may either induce asthma-like features or increase asthma severity. Third, mitochondria-targeted therapies appear effective in preventing or reversing asthma features. Importantly, mitochondrial dysfunction in airway epithelial cells appears to be a powerful trigger for airway remodeling that is independent of cellular inflammation. This is clinically relevant to the obese–asthma phenotype, with exaggerated symptoms despite apparently low levels of inflammation, and poor response to antiinflammatory treatment. In summary, mitochondrial dysfunction is a common thread tying together the twin epidemics of obesity and asthma. Environmental and lifestyle factors leading to primary mitochondrial dysfunction may be increasing the risk for either disease. Further, secondary mitochondrial dysfunction emerging from the pathogenesis of either obesity or asthma may increase the risk of the other. Mitochondrial health–centric strategies may be relevant to prevention and treatment of both obesity and asthma, and should be actively considered.