Leptin, adiponectin and pulmonary diseases

Abstract

Adipose tissue produces leptin and adiponectin - energy-regulating adipokines that may also play a role in inflammatory pulmonary conditions, as suggested by some murine studies. Leptin and adiponectin and their respective receptors are expressed in the human lung. The association between systemic or airway leptin and asthma in humans is currently controversial, particularly among adults. The majority of the evidence among children however suggests that systemic leptin may be associated with greater asthma prevalence and severity, particularly among prepubertal boys and peripubertal/postpubertal girls. Systemic and airway leptin concentrations may also be disproportionately higher in chronic obstructive pulmonary disease (COPD) patients, particularly among women, and reflect greater airway inflammation and disease severity. Quite like leptin, the association between systemic and airway adiponectin and asthma in humans is also controversial. Some but not all studies, demonstrate that serum adiponectin concentrations are protective against asthma among premenopausal women and peripubertal girls. On the other hand, serum adiponectin concentrations are inversely associated with asthma severity among boys but positively associated among men. Further, systemic and airway adiponectin concentrations are higher in COPD patients than controls, as demonstrated by case-control studies of men. Systemic adiponectin is also positively associated with lung function in healthy adults but inversely associated with lung function in subjects with COPD. It is therefore possible that pro-inflammatory effects of adiponectin dominate under certain physiologic conditions and anti-inflammatory effects under others. The adipokine-lung disease literature has critical gaps that include a lack of adequately powered longitudinal or weight-intervention studies; inadequate adjustment for confounding effect of obesity; and unclear understanding of potential sex interactions. It is also uncertain whether adipokine derangements precede pulmonary disease or are a consequence of it. Future research will determine whether modulation of adipokines, independent of BMI, may allow novel ways to prevent or treat inflammatory pulmonary conditions.

Figure 1

A schematic representation of the suggested role for leptin in murine asthma, based upon the work by Shore et al. [21]. Although these findings were not entirely reproduced in a human interventional study of mild atopic asthma [37], epidemiologic evidence suggests that greater serum leptin concentrations are associated with more severe asthma, particularly among prepubertal boys and peripubertal/postpubertal girls [31, 32].

Figure 2

A schematic representation of the suggested role for adiponectin in murine asthma, based upon the work by Shore et al. [86]. Although these findings were not entirely reproduced in a human interventional study of mild atopic asthma [37], epidemiologic evidence suggests that lower serum adiponectin concentrations are associated with increased odds for asthma, particularly among peripubertal girls and premenopausal women [34, 35]. Figure as originally published in ‘A. Sood, E. Dominic, C. Qualls, M.W. Steffes, B. Thyagarajan, L.J. Smith, C.E. Lewis, D.R. Jacobs, Jr., Serum Adiponectin is Associated with Adverse Outcomes of Asthma in Men but Not in Women, Front Pharmacol 2 (2011) 55’ is reproduced with permission [71].

Figure 3

A schematic representation of the suggested role for adiponectin in murine emphysema, based upon the work by Nakanishi et al. [90]