Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice

Shore, Stephanie A.; Terry, Raya D.; Flynt, Lesley; Xu, Aimin; Hug, Christopher

doi:10.1016/j.jaci.2006.04.021

Cited by 281 publications

(278 citation statements)

References 58 publications

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“…Previous studies have investigated the functional role of adiponectin and leptin in asthma: in allergic mouse models of asthma, leptin increases and adiponectin decreases airway reactivity (22,23). We found a significant relationship between visceral fat leptin expression and airway reactivity.…”

Section: Discussionmentioning

confidence: 49%

Obesity and Asthma

Sideleva¹,

Suratt²,

Black³

et al. 2012

Am J Respir Crit Care Med

298

159

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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 ¼ 20.8; 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.

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Section: Discussionmentioning

confidence: 49%

Obesity and Asthma

Sideleva¹,

Suratt²,

Black³

et al. 2012

Am J Respir Crit Care Med

298

159

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“…Murine studies have, however, shown that this association is bidirectional, whereby exogenous adiponectin attenuates airway changes of asthma and allergen-induced bronchoprovocation decreases adiponectin concentrations (22). Although current human data remain inconclusive, our previous cross-sectional study shows that low serum adiponectin concentrations are associated with increased odds for prevalent asthma among women and not men (6).…”

mentioning

confidence: 80%

“…A causative role for adiponectin in asthma has been better established in mice than in humans (22). Murine studies have, however, shown that this association is bidirectional, whereby exogenous adiponectin attenuates airway changes of asthma and allergen-induced bronchoprovocation decreases adiponectin concentrations (22).…”

mentioning

confidence: 99%

Low Serum Adiponectin Predicts Future Risk for Asthma in Women

Sood¹,

Qualls

Schuyler³

et al. 2012

Am J Respir Crit Care Med

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Rationale: Our previous cross-sectional study showed that serum adiponectin is inversely associated with asthma among women. However, it is not known if serum adiponectin predicts future development of asthma or if asthma affects subsequent serum adiponectin concentrations among women. Objectives: To determine longitudinal association between serum adiponectin and incident asthma among women. Methods: We used data from examinations at Years 10, 15, and 20 of the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. In our primary analysis, the association of CARDIA Year 15 serum adiponectin concentration with Year 20 incident asthma was evaluated. In our secondary analysis, the converse direction, that is, the association of CARDIA Year 10 prevalent asthma with Year 15 serum adiponectin, was evaluated, using logistic regression techniques. Measurements and Main Results: Our primary analysis included 1,450 women, mostly premenopausal. Multivariable analyses demonstrated that the lowest tertile of Year 15 serum adiponectin concentration (,7 mg/L) predicted significantly higher risk for incident asthma at Year 20 among women (odds ratio, 2.07; 95% confidence interval, 1.05, 4.10), and particularly among current smokers (interaction P ¼ 0.051). Further, low serum adiponectin was more important than body mass index in predicting the risk for incident asthma among women. We also showed that the converse relationship was not true; that is, Year 10 prevalent asthma did not predict Year 15 serum adiponectin concentrations in women. Conclusions: Serum adiponectin affects future risk for asthma in women and not vice versa. Measures that raise systemic adiponectin concentrations may lead to newer ways to prevent asthma among women, particularly among those who smoke.Keywords: incident asthma; obesity; adiponectin; adipokine; women In 2005, more than 21 million people in the United States were estimated to be affected by asthma, amounting to 7.6% of the total population (1). Between 1980 and 1996, the prevalence of, and morbidity trends related to, asthma increased in the United States (2, 3). It is now well established that asthma is related to adiposity, particularly among women. Adipokines, proteins produced by adipose tissue, may regulate systemic inflammation and play a role in asthma (4-7). Adiponectin is one such adipokine with predominantly antiinflammatory effects. Adiponectin inhibits proinflammatory cytokines and endothelial adhesion molecules and induces antiinflammatory cytokines (8-11). Further, adiponectin regulates the proliferation and function of inflammatory cells including NK cells and T lymphocytes (12, 13).Although visceral adipocytes are the most important source of adiponectin, serum adiponectin concentrations are reduced in obese subjects (14,15). One possible explanation is that hypoxia-related necrosis of adipocytes activates macrophages in obese subjects (16). These activated macrophages produce tumor necrosis factor-a and IL-6, which in turn may directly inhibit the local production o...

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“…Some of the observed beneficial effects of adiponectin in the airways [13,14] may be related to its anti-inflammatory effects, particularly its effects on macrophages, although adiponectin also has proinflammatory effects [18][19][20]. Adiponectin decreases the ability of LPS or Toll-like receptor activation to elicit TNF and IL-6 production from macrophages [21][22][23][24] and reduces eotaxin expression in bone marrow derived macrophages stimulated with TNF and IL-4 [12].…”

Section: Introductionmentioning

confidence: 99%

“…Two allergen sensitization and challenge protocols were employed. The first, an acute challenge protocol, was similar to that used in a previous study in which we examined the effects of adiponectin administered by miniAlzet pumps [13] and was used as a proof of concept that adiponectin overexpressed in this manner would be effective. The second protocol, a chronic challenge protocol, results in allergic airways inflammation and goblet cell metaplasia, that is dependent on mast cells [31], as is allergic asthma in humans, whereas the acute protocol requires T cells but not mast cells [32].…”

Section: Introductionmentioning

confidence: 99%

Impact Of Adiponectin Overexpression On Allergic Airways Responses In Mice

Verbout¹,

Hug²,

Si³

et al. 2010

C103. Dietary Influences for Asthma and Chronic Obstructive Pulmonary Disease: It's All About What You Eat

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Obesity is an important risk factor for asthma. Obese individuals have decreased circulating adiponectin, an adipose-derived hormone with anti-inflammatory properties. We hypothesized that transgenic overexpression of adiponectin would attenuate allergic airways inflammation and mucous hyperplasia in mice. To test this hypothesis, we used mice overexpressing adiponectin (Adipo Tg). Adipo Tg mice had marked increases in both serum adiponectin and bronchoalveolar lavage (BAL) fluid adiponectin. Both acute and chronic ovalbumin (OVA) sensitization and challenge protocols were used. In both protocols, OVA-induced increases in total BAL cells were attenuated in Adipo Tg versus WT mice. In the acute protocol, OVA-induced increases in several IL-13 dependent genes were attenuated in Adipo Tg versus WT mice, even though IL-13 per se was not affected. With chronic exposure, though OVA-induced increases in goblet cells numbers per millimeter of basement membrane were greater in Adipo Tg versus WT mice, mRNA abundance of mucous genes in lungs was not different. Also, adiponectin overexpression did not induce M2 polarization in alveolar macrophages. Our results indicate that adiponectin protects against allergen-induced inflammatory cell recruitment to the airspaces, but not development of goblet cell hyperplasia.

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Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice

Cited by 281 publications

References 58 publications

Obesity and Asthma

Obesity and Asthma

Low Serum Adiponectin Predicts Future Risk for Asthma in Women

Impact Of Adiponectin Overexpression On Allergic Airways Responses In Mice

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