Obesity, adipokines, and lung disease

Abstract

This review summarizes the state of the current literature relating to the associations of lung disease on obesity and adipokines (proteins produced by adipose tissue) in humans. Obesity is an independent risk factor for asthma. Recent studies suggest that obesity is also an independent risk factor for chronic airflow obstruction, as is seen with chronic obstructive pulmonary disease (COPD). The mechanistic basis for these associations in humans is not established, although a possible role for adipokines has been invoked. Leptin, a proinflammatory adipokine, and adiponectin, an anti-inflammatory adipokine, are causally associated with asthma in mice. Although human studies are currently inconclusive, high-serum leptin and low-serum adiponectin concentrations predict asthma, independent of obesity, in select population groups, such as premenopausal women in the United States. In contradistinction, low-serum leptin and high-serum adiponectin concentrations are associated with stable COPD, although these associations are likely confounded by fat mass. Interestingly, leptin may promote systemic and airway inflammation in stable COPD patients. On the other hand, COPD may upregulate systemic and lung adiponectin expression. The precise mechanism and significance of the associations between these adipokines and lung disease at the current stage is confusing and frankly paradoxical in places. This area of research needs additional study that may open up novel therapeutic strategies for these lung diseases.

Fig. 1.

Maximal and tidal flow-volume loops for a series of age-matched women: a lean woman with normal lung function, an obese woman with normal lung function, a lean woman with chronic obstructive pulmonary disease (COPD) (forced expiratory volume in 1 s: 46% predicted), and an obese woman with COPD (forced expiratory volume in 1 s: 45% predicted). Inner tidal loops are shown at rest (solid inner loops) and at ventilations of ∼32 l/min (dashed loops), the latter corresponding to the symptom-limited peak of exercise for both women with COPD. While the end-expiratory lung volume was decreased during exercise in the healthy lean woman, the other women experienced dynamic pulmonary hyperinflation (leftward arrows). The dynamic hyperinflation in women with both obesity and COPD was greater than that for the women with either condition alone. Additional flow and volume constraints on tidal volume expansion in the women with COPD limited the peak ventilation that could be attained during exercise. In women with COPD, a critically reduced inspiratory reserve volume limited any further increase in tidal volume during exercise and resulted in severe exertional dyspnea. Ratings of dyspnea intensity using the modified 10-point Borg scale are shown at comparable ventilations during exercise. [Reproduced with permission from Franssen et al. (25).]