The multifaceted role of eosinophils in adipose tissue: from metabolism to allergy

Abstract

Obesity has reached epidemic proportions worldwide, with some of the greatest severity in the United States. The most recent data reports ~70% of the American population is overweight (BMI ≥ 25 kg/m2) and ~35% obese (BMI ≥30 kg/m2). Obesity is a metabolic disorder leading to increased risk for cardiovascular disease, type 2 diabetes, asthma, certain cancers, and various other diseases. A hallmark of obesity is adipose tissue (AT) inflammation and AT dysfunction. It is important to understand how immune cells accumulate in AT and regulate inflammation. We used CCR2-/- mice to study macrophage chemotaxis to AT, and also discovered CCR2-/- regulates chemotactic factors that upregulate AT eosinophil accumulation. Previous studies suggested that directly manipulating eosinophils (particularly in AT) could impart beneficial effects in obese subjects. Thus we developed an interventional treatment model of restoring obese AT eosinophils to higher levels of lean AT by injection of rIL5. AT eosinophils were successfully increased with rIL5, but there was no reduction in obesity and its comorbidities. Lastly, we discovered that repeated exposure to a foreign substance such as bovine serum albumin (BSA) could greatly increase AT eosinophils. While there were no metabolic improvements in mice chronically exposed to BSA, we have evidence to believe AT is capable of mounting a type 2 allergic response to antigens similar to the lung of an asthmatic, resulting in this large increase in AT eosinophils. Future studies will determine whether the AT eosinophilia following BSA exposure feeds back to the lung in allergic models, increasing both incidence and severity. Such studies will help in explaining the clinical link between obesity and allergic conditions such as asthma. In conclusion, we have found that restoring AT eosinophils to either physiological levels or super-physiological levels during obesity is not able to improve metabolic fitness (e.g. weight gain, glucose intolerance). Furthermore, we may have discovered a novel site of allergy that could offer insights and treatment opportunities for obese subjects that have increased difficulty with allergic disease.