Targeting Obesity, Insulin Resistance and Type 2 Diabetes with Immunotherapy: The Challenges Ahead

Abstract

Obesity is associated with chronic low‐grade tissue inflammation The prevalence of obesity and insulin resistance is rapidly increasing worldwide. These growing lifestyle-related diseases are problematic and strongly correlated with several associated disorders, such as dyslipidemia, hypertension and glucose intolerance [1,2]. Obesity is considered an independent risk factor for stroke, myocardial infarction, peripheral artery disease and Type 2 diabetes [3,4]. A recent meta-analysis reported that obesity is significantly associated with higher rates of mortality overall [5], therefore, measures against obesity must be taken. A number of studies have reported that levels of adipose tissue macrophages (ATMs) are elevated in obese epididymal and subcutaneous fat tissue [1,6–8]. Infiltration by ATMs into fat tissues is an essential step in the pathogenesis of metabolic diseases [9,10]. ATMs are a basic source of inflammatory regulators and mediators, including TNF-a, IL-1, IL-6, MCP-1 and matrix metalloproteinases, that contribute to insulin resistance in adipocytes [11,12]. It has been reported that CD4Foxp3 T cells can induce the anti-inflammatory M2 macrophage, which secretes IL-10 and protects against insulin resistance [13]. Obesity and insulin resistance are closely associated with chronic low-grade tissue inflammation, therefore, immunotherapy can potentially be used to combat these diseases. A number of in vitro, in vivo and clinical research studies have revealed the relationship between obesity, insulin resistance and immune system abnormalities, and also demonstrated the efficacy of immunotherapy [14–21].