Adiponectin Deficiency Increases Allergic Airway Inflammation and Pulmonary Vascular Remodeling

Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, CNY 8301, 149 13th Street, Charlestown, MA 02129, USA.
American Journal of Respiratory Cell and Molecular Biology (Impact Factor: 3.99). 02/2009; 41(4):397-406. DOI: 10.1165/rcmb.2008-0415OC
Source: PubMed


Obesity is associated with an increased incidence and severity of asthma, as well as other lung disorders, such as pulmonary hypertension. Adiponectin (APN), an antiinflammatory adipocytokine, circulates at lower levels in the obese, which is thought to contribute to obesity-related inflammatory diseases. We sought to determine the effects of APN deficiency in a murine model of chronic asthma. Allergic airway inflammation was induced in APN-deficient mice (APN(-/-)) using sensitization without adjuvant followed by airway challenge with ovalbumin. The mice were then analyzed for changes in inflammation and lung remodeling. APN(-/-) mice in this model develop increased allergic airway inflammation compared with wild-type mice, with greater accumulation of eosinophils and monocytes in the airways associated with elevated lung chemokine levels. Surprisingly, APN(-/-) mice developed severe pulmonary arterial muscularization and pulmonary arterial hypertension in this model, whereas wild-type mice had only mild vascular remodeling and comparatively less pulmonary arterial hypertension. Our findings demonstrate that APN modulates allergic inflammation and pulmonary vascular remodeling in a model of chronic asthma. These data provide a possible mechanism for the association between obesity and asthma, and suggest a potential novel link between obesity, inflammatory lung disease, and pulmonary hypertension.

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    • "Humoral interactions, e.g. leptin resistance contributing to hypoventilation [29], and a major role of adiponectine in the pathophysiology of PAH and asthma have been discussed [25]–[28]. However, it remains unclear whether body fat contributes to functional abnormalities in the cardiopulmonary system via an underlying systemic inflammatory process or if ventilation and pulmonary circulation are only influenced by the mechanical influences of increased body fat [30]. "
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    ABSTRACT: BackgroundThe prevalence of obesity is rising. Obesity can lead to cardiovascular and ventilatory complications through multiple mechanisms. Cardiac and pulmonary function in asymptomatic subjects and the effect of structured dietary programs on cardiac and pulmonary function is unclear.ObjectiveTo determine lung and cardiac function in asymptomatic obese adults and to evaluate whether weight loss positively affects functional parameters.MethodsWe prospectively evaluated bodyplethysmographic and echocardiographic data in asymptomatic subjects undergoing a structured one-year weight reduction program.Results74 subjects (32 male, 42 female; mean age 42±12 years) with an average BMI 42.5±7.9, body weight 123.7±24.9 kg were enrolled. Body weight correlated negatively with vital capacity (R = −0.42, p<0.001), FEV1 (R = −0.497, p<0.001) and positively with P 0.1 (R = 0.32, p = 0.02) and myocardial mass (R = 0.419, p = 0.002). After 4 months the study subjects had significantly reduced their body weight (−26.0±11.8 kg) and BMI (−8.9±3.8) associated with a significant improvement of lung function (absolute changes: vital capacity +5.5±7.5% pred., p<0.001; FEV1+9.8±8.3% pred., p<0.001, ITGV+16.4±16.0% pred., p<0.001, SR tot −17.4±41.5% pred., p<0.01). Moreover, P0.1/Pimax decreased to 47.7% (p<0.01) indicating a decreased respiratory load. The change of FEV1 correlated significantly with the change of body weight (R = −0.31, p = 0.03). Echocardiography demonstrated reduced myocardial wall thickness (−0.08±0.2 cm, p = 0.02) and improved left ventricular myocardial performance index (−0.16±0.35, p = 0.02). Mitral annular plane systolic excursion (+0.14, p = 0.03) and pulmonary outflow acceleration time (AT +26.65±41.3 ms, p = 0.001) increased.ConclusionEven in asymptomatic individuals obesity is associated with abnormalities in pulmonary and cardiac function and increased myocardial mass. All the abnormalities can be reversed by a weight reduction program.
    PLoS ONE 09/2014; 9(9):e107480. DOI:10.1371/journal.pone.0107480 · 3.23 Impact Factor
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    • "These results were supported by another study using a chronic experimental asthma model in mice which demonstrated that allergic airway inflammation was increased in adiponectin-deficient mice compared with wild-type mice. These mice showed a greater accumulation of eosinophils and monocytes in the airways.37 "
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    ABSTRACT: Increasing epidemiological data identify a link between obesity and asthma incidence and severity. Based on experimental data, it is possible that shared inflammatory mechanisms play a role in determining this linkage. Although controversial, the role of adipokines may be central to this association and the maintenance of the asthma phenotype. While leptin and adiponectin have a causal link to experimental asthma in mice, data in humans are less conclusive. Recent studies demonstrate that adipokines can regulate the survival and function of eosinophils and that these factors can affect eosinophil trafficking from the bone marrow to the airways. In addition, efferocytosis, the clearance of dead cells, by airway macrophages or blood monocytes appears impaired in obese asthmatics and is inversely correlated with glucocorticoid responsiveness. This review examines the potential mechanisms linking obesity to asthma.
    Allergy, asthma & immunology research 05/2014; 6(3):189-195. DOI:10.4168/aair.2014.6.3.189 · 2.43 Impact Factor
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    • "Exposure to allergen may also affect adiponectin expression. Studies often utilize OVA (ovalbumin), the main protein in egg white, to induce sensitization of study mice for investigating respiratory allergic reaction such as asthma mechanism (Shore et al., 2005, 2006; Gueders et al., 2009; Medoff et al., 2009). In Shore et al. (2006) study, lower adiponectin concentration in serum was found in OVA-exposed mice compared to those non-exposed. "
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    ABSTRACT: This study investigates whether allergen exposure elevates the risk of diabetes or cardiovascular diseases using acute OVA (Ovalbumin) allergen exposure model. We hypothesize that exposure to allergen can induce adipose tissue inflammation and affect adiponectin levels. An intranasal challenge with OVA male C57BL/6 mice was performed at dose of 6.25, 12.5, 25, 50 and 100μg, and compared to which challenge with PBS (Phosphate Buffered Saline). Results showed that acute OVA exposure did not only cause airway inflammation in study mice, but also decrease serum adiponectin levels with a dose-response effect. When examining the gonadal adipose tissues, there was no significantly difference of adiponectin mRNA in OVA challenged mice compared to those PBS challenged, but lower inguinal adiponectin mRNA expression was found compared to those PBS-challenged, and has a good relationship with the serum adiponectin. Inguinal adipose tissues of OVA challenged mice, had significantly lower adipose tissue weight, and higher TNF-α expression without statistical significance. Our data indicate that acute OVA exposure appears to affect the characteristics of adipose tissues, and change the adiponectin levels in serum and adipose tissues. Allergen exposure may be considered a potential risk factor for presenting diabetes or cardiovascular diseases.
    Toxicology Letters 09/2013; 223(1). DOI:10.1016/j.toxlet.2013.08.019 · 3.26 Impact Factor
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