Adiponectin, Leptin, and Resistin in Asthma: Basic Mechanisms through Population Studies

Abstract

Adipokines, factors produced by adipose tissue, may be proinflammatory (such as leptin and resistin) or anti-inflammatory (such as adiponectin). Effects of these adipokines on the lungs have the potential to evoke or exacerbate asthma. This review summarizes basic mechanistic data through population-based and clinical studies addressing the potential role of adipokines in asthma. Augmenting circulating concentrations of adiponectin attenuates allergic airway inflammation and airway hyperresponsiveness in mice. Murine data is supported by human data that suggest that low serum adiponectin is associated with greater risk for asthma among women and peripubertal girls. Further, higher serum total adiponectin may be associated with lower clinical asthma severity among children and women with asthma. In contrast, exogenous administration of leptin results in augmented allergic airway hyperresponsiveness in mice. Alveolar macrophages obtained from obese asthmatics are uniquely sensitive to leptin in terms of their potential to augment inflammation. Consistent with this basic mechanistic data, epidemiologic studies demonstrate that higher serum leptin is associated with greater asthma prevalence and/or severity and that these associations may be stronger among women, postpubertal girls, and prepubertal boys. The role of adipokines in asthma is still evolving, and it is not currently known whether modulation of adipokines may be helpful in asthma prevention or treatment.

The Serum Level of Leptin in Patients with Obesity: Asthmatic and Non-Asthmatic Children

“…It seems that the association between obesity and asthma is complex and multifaceted and is likely explained by many mechanisms. Recently, a distinctive role is suggested for leptin in the prognosis of asthma in patients with obesity and also a link between leptin and asthma is suggested by some studies (3,16,17).…”

“…It is suggested that during the development of obesity, hypertrophy of the adipose tissue results in local tissue hypoxia, adipocyte necrosis, and macrophage recruitment. These factors, in association with each other, lead to toll-like receptor signaling via fatty acids, and subsequently, result in the gen- Leptin is a 16-kD protein derived from the obese gene and is expressed predominantly in adipocytes (16). It is considered that many factors affecting the serum leptin level including gender, age, puberty, BMI, breast feeding, and steroid therapy (12,18,19).…”

Endocrine regulation of airway contractility is overlooked

“…For the purpose of clarity, the endocrine regulation of the lung immune system is not addressed in detail in the present review. Readers are referred to recent reviews that are covering this particular topic (Townsend et al 2012a, Wright 2012, Sood & Shore 2013.…”

“…Leptin rather acts through the central nervous system to attenuate the constitutive muscarinic activation of ASM that emanates from the parasympathetic inputs of the vagi However, the effect of leptin in the context of asthma is not clear. This subject has been reviewed recently (Sood & Shore 2013). The level of leptin in the blood and adipose tissue is generally elevated in asthmatics.…”

“…However, the method of leptin delivery was different between these studies; i.e. i. Adiponectin The role of adiponectin in asthma has been reviewed recently (Sood & Shore 2013). Adiponectin is an adipokine that is mainly produced by visceral fat.…”