Obesity and asthma: an inflammatory disease of adipose tissue not the airway

Abstract

Rationale: Obesity is a major risk factor for asthma; the reasons for this are poorly understood, although it is thought that inflammatory changes in adipose tissue in obesity could contribute to airway inflammation and airway reactivity in individuals who are obese.

Objectives: To determine if inflammation in adipose tissue in obesity is related to late-onset asthma, and associated with increased markers of airway inflammation and reactivity.

Methods: We recruited a cohort of obese women with asthma and obese control women. We followed subjects with asthma for 12 months after bariatric surgery. We compared markers in adipose tissue and the airway from subjects with asthma and control subjects, and changes in subjects with asthma over time.

Measurements and main results: Subjects with asthma had increased macrophage infiltration of visceral adipose tissue (P < 0.01), with increased expression of leptin (P < 0.01) and decreased adiponectin (p < 0.001) when controlled for body mass index. Similar trends were observed in subcutaneous adipose tissue. Airway epithelial cells expressed receptors for leptin and adiponectin, and airway reactivity was significantly related to visceral fat leptin expression (rho = -0.8; P < 0.01). Bronchoalveolar lavage cytokines and cytokine production from alveolar macrophages were similar in subjects with asthma and control subjects at baseline, and tended to increase 12 months after surgery.

Conclusions: Obesity is associated with increased markers of inflammation in serum and adipose tissue, and yet decreased airway inflammation in obese people with asthma; these patterns reverse with bariatric surgery. Leptin and other adipokines may be important mediators of airway disease in obesity through direct effects on the airway rather than by enhancing airway inflammation.

Figure 1.

Relationship between visceral fat leptin expression and airway reactivity in participants with asthma at baseline (nine participants had measurement of methacholine reactivity and visceral fat isolation at baseline). rho = −0.8, P = 0.0096 for Spearman’s correlation. Repeat analysis dropping outlier with highest PC₂₀: rho = −0.74; P = 0.037.

Figure 2.

Immunohistochemistry showing expression of the macrophage marker CD68 (red) in adipose tissue. Blue staining is DAPI and green staining is BS-1 lectin. (a) CD68 staining alone in visceral adipose tissue of participant with asthma. (b) Composite figure of visceral adipose tissue of participant with asthma. (c) Subcutaneous adipose tissue from participant with asthma before surgery. (d) Subcutaneous adipose tissue from participant with asthma after surgery. Also shown are representative sections from (e) control participants and (f) CD68 staining control.

Figure 3.

Serum adipokines in 15 control subjects and 11 participants with asthma at baseline, and in 11 participants with asthma at 12 months. *P < 0.05. MCP = monocyte chemotactic protein.

Figure 4.

Adipokines and cytokines in bronchoalveolar lavage (BAL) fluid from control subjects (n = 15) and participants with asthma at baseline (n = 11) and participants with asthma 12 months after surgery (n = 11). *P < 0.05. Of note, y axis is on a log scale. MCP = monocyte chemotactic protein; TNF = tumor necrosis factor.

Figure 5.

Cytokine production from (A) untreated and (B) LPS-stimulated airway macrophages before surgery (controls subjects, n = 11; subjects with asthma, n = 5) and 12 months after surgery (participants with asthma, n = 5). *P < 0.05, **P < 0.01. Of note, y axis is on a log scale. TNF = tumor necrosis factor.