Obesity, Metabolic Syndrome, and Airway Disease

Abstract

SYNOPSIS Common pathophysiological mechanisms are increasingly being recognized between obesity, metabolic dysfunction, and airway disease. Obesity increases asthma risk or severity, in multiple studies across the globe. Metabolic changes of obesity such as diabetes or insulin resistance are associated with asthma as well as poorer lung function. Insulin resistance has also been found to increase asthma risk independent of body mass. Conversely, asthma has been associated with abnormal glucose and lipid metabolism, insulin resistance, and obesity. These bidirectional and dose-dependent associations suggest common unifying molecular processes that contribute to these seemingly disparate diseases. Reduced mitochondrial mass and/or function is increasingly recognized as one such mechanism that has been causally associated with insulin resistance, obesity and asthma, while conversely, restoration of mitochondrial numbers and function can lead to recovery of normal bioenergetics with reversal of disease features. Here, we review current understanding of how dietary and lifestyle factors lead to changes in mitochondrial metabolism and cellular bioenergetics, inducing various components of the cardiometabolic syndrome as well as airway disease. We provide an overview of and evidence for potentially useful mitochondria-targeted therapies, and discuss the emerging use of mesenchymal stem cells as mitochondrial donors, in the context of asthma.

Mitochondrial Function in Allergic Disease

“…Intuitively, the administration of antioxidants in the case of MetS/asthma should have been effective, as these are mtROS disorders. However, administration of alpha tocopherol and vitamin C has not been successful [2,72,73]**. This is probably because the surge of mtROS is too high to be countered by antioxidants or that the oxidative damage sustained by mitochondria is too far gone to be helped by belated quenching of ROS.…”

“…It is important to note that untargeted quenching of ROS could achieve different results in different cells. While increased mtROS is harmful in airway smooth muscle cells and fibroblasts leading to mitochondrial dysfunction and asthma, fluctuating mtROS levels in homing immune cells, such as Tregs, promote fatty acid metabolism and consequent antiinflammatory functions that should be left undisturbed [72]**. Therefore, cell type-specific ROS quenching is called for in this approach to therapy.…”

Rejuvenating cellular respiration for optimizing respiratory function: targeting mitochondria

“…The mitotoxic effects of metabolic products such 13-S-hydroxyoctadecadienoic acid and asymmetric dimethyl arginine (ADMA) appear to be critical in epithelial injury (5,6,77,78). These may be endogenously generated in response to inflammation or be exogenously delivered in the case of systemic metabolic diseases that precipitate asthma (2,3,117). Overall, most lines of data converge to show that mitochondrial dysfunction is an important part of epithelial fragility in asthma.…”

Impact of Obesity on Adipokines, Inflammatory Cytokines and Clinical Symptoms Control in Asthmatic Subjects

“…However, systemic inflammation increase the risk for cardiovascular disorders in bronchial asthma [12]. Moreover, neutrophilic airway inflammation, increased resistance for corticosteroids and increased morbidity are criteria for an association between obesity and asthma [13][14][15].…”