Immunometabolism in Obese Asthmatics: Are We There Yet?

Abstract

Obesity is now recognised as a worldwide epidemic. The recent International Association for the Study of Obesity/International Obesity Taskforce (IASO/IOTF) analysis estimates that approximately 1.0 billion adults are currently overweight and a further 475 million are obese. Obesity has huge psychosocial impact with obese children and adolescents facing discrimination and stigmatization in many areas of their lives leading to body dissatisfaction, low self-esteem and depression. Indeed, obesity is recognised as an important risk factor for the development of several chronic diseases such as hypertension, cancer, asthma and metabolic syndrome. Chronic low grade systemic inflammation is considered as a hallmark of obesity and may possibly explain the link between obesity and chronic disease, in particular the increased incidence, prevalence and severity of asthma in obese individuals. There is now strong evidence for infiltration of immune and inflammatory cells into adipose tissue that drives systemic inflammation and subsequent end organ damage. In addition to adipocytes, the key adipose tissue resident immune cells are macrophages and mast cells. Immunometabolism, as an emerging field of investigation, explores the pivotal role of these immune cells in translating immunological changes to metabolic effects in obesity. Abundance of free fatty acids, along with other inflammatory cytokines shift the balance of metabolic homeostasis to pro-inflammatory status by influencing the development of inflammatory cell lineage, which, further exhibits distinct functional phenotypes. There is emerging evidence for macrophage activation and functional polarization of an anti-inflammatory M2 phenotype towards a pro-inflammatory M1 phenotype of macrophages in obese adipose tissue. Similarly, studies in both obese humans and murine models reveal the pathognomic presence of an increased number of mast cells in visceral adipose tissue. These suggest a possible contribution of mast cells to the unique metabolome of obese asthma. This review examines proposed multilevel interactions between metabolic and immune systems in obese asthmatics that underlie the negative effects of obesity and may offer significant therapeutic promise.

Inflammation, Metabolic Dysregulation, and Pulmonary Function among Obese Urban Adolescents with Asthma

“…Together, our findings suggest that immunometabolism may play a role among obese subjects with asthma (48). The association of monocytes with HDL levels and Th cells with insulin resistance begins to elucidate the complex interactive relationship between obesity-mediated metabolic dysregulation with immune cell activation, which contributes to obesityrelated asthma via varied pathways, which may underlie the heterogeneity of the disease.…”

Increased asthma and adipose tissue inflammatory gene expression with obesity and Inuit migration to a western country

“…Both asthma and obesity can be associated with chronic low-grade systemic inflammation involving acute phase proteins such as C-reactive protein and proinflammatory cytokines such as IL-6 and IL-1b, which may be driven by adipose tissue inflammation [7]. Macrophages with a proinflammatory phenotype, termed M1, produce inflammatory cytokines such as IL-6 and IL-1b, whereas those with an antiinflammatory (M2) phenotype are CD163 positive [5]. Caloric excess, that is typical of a western diet, has been shown in animal models to induce both systemic inflammation and adipose tissue inflammation, involving an increase in the number of M1 macrophages in the stromal vascular fraction of adipose tissue.…”

Asthma and diabetes: Does treatment with metformin improve asthma?

“…The metabolic complications of obesity – insulin resistance, the metabolic syndrome and diabetes – likely play an important role in the pathophysiology of ‘obese asthma’ . The association between obesity and asthma is greater in the presence of insulin resistance .…”