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. 1. Introduction Obesity is an important risk factor for asthma. Obesity increases the prevalence, the incidence, and possibly the severity of asthma, while weight loss improves many asthma outcomes in the obese [1, 2]. In addition, standard asthma therapeutic agents are less effective in obese versus lean asthmatics [3, 4]. Adiponectin is an adipocyte-derived hormone that declines in obesity [5]. Loss of adiponectin in obesity appears to have important functional consequences. In animal models, adiponectin deficiency exacerbates several obesity-related conditions, including insulin resistance and atherosclerosis [6, 7]. In obese human subjects, serum adiponectin levels are inversely correlated with the risk of type 2 diabetes, atherosclerosis, and hypertension [8–10]. Some, but not all, epidemiological studies suggest that obesity-related declines in adiponectin may also contribute to obesity-related asthma. For example, in a cohort of premenopausal women, the risk of asthma was greatest in subjects in the lowest tertile of serum adiponectin [11]. Similarly, in C57BL/6 mice, adiponectin deficiency worsens airway eosinophilia and macrophage recruitment induced by chronic allergen challenge [12]. In addition, we have shown that in lean Balb/C mice,
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