Adipose Tissue Inflammation and Pulmonary Dysfunction in Obesity

Abstract

Obesity is a chronic disease caused by an excess of adipose tissue that may impair health by altering the functionality of various organs, including the lungs. Excessive deposition of fat in the abdominal area can lead to abnormal positioning of the diaphragm and consequent reduction in lung volume, leading to a heightened demand for ventilation and increased exposure to respiratory diseases, such as chronic obstructive pulmonary disease, asthma, and obstructive sleep apnoea. In addition to mechanical ventilatory constraints, excess fat and ectopic deposition in visceral depots can lead to adipose tissue dysfunction, which promotes metabolic disorders. An altered adipokine-secretion profile from dysfunctional adipose tissue in morbid obesity fosters systemic, low-grade inflammation, impairing pulmonary immune response and promoting airway hyperresponsiveness. A potential target of these adipokines could be the NLRP3 inflammasome, a critical component of the innate immune system, the harmful pro-inflammatory effect of which affects both adipose and lung tissue in obesity. In this review, we will investigate the crosstalk between adipose tissue and the lung in obesity, highlighting the main inflammatory mediators and novel therapeutic targets in preventing pulmonary dysfunction.

Keywords: adipokines; adipose tissue; crosstalk; inflammasome; lung; obesity; respiratory diseases.

Figure 1

Crosstalk between dysfunctional adipose tissue and respiratory epithelium in the lung. Insulin resistance, adipocyte hypertrophy, and hypoxia alter adipokine secretion from dysfunctional adipose tissue, promoting NLRP3 inflammasome activation and IL-1β secretion. Activation of IL-1β signalling in the lung increases the expression of pro-inflammatory cytokines (e.g., IL-23, IL-5, IL-13), promoting the activity of immune cells (e.g., T-helper cells, eosinophils, macrophages) and leading to lung inflammation.

Figure 2

Effects of obesity on pulmonary function and therapeutic strategies for the treatment of lung diseases. Insulin resistance and adipocyte hypertrophy induce adipose tissue inflammation. Excess of adipose tissue is responsible for mechanical obstruction of lung airways, promoting development of asthma, OSAS, COPD, and OHS, which are responsible for hypoxia. Both hypoxia and adipose tissue inflammation foster activation of the NLRP3 inflammasome, increasing levels of pro-inflammatory cytokines (IL-1β, IL-5, IL-13, IL-17) and promoting development of lung diseases. Improvement in the respiratory function in people with obesity and lung disease could be achieved through therapeutic intervention for weight loss or through pharmacological strategies able to target the inflammasome and its downstream cytokines.