Review Article

Roles of the Chemokine System in Development of Obesity, Insulin Resistance, and Cardiovascular Disease

Figure 1

Obesity contributes to development of diabetes and cardiovascular disease. Adipose tissue is composed of two main cell types, adipocytes and stromovascular mononuclear cells (i.e., resident leukocytes). Adipose tissue macrophages (ATMs) are the most frequent leukocyte subtype in fat tissues. Normal adipose tissue is populated with the alternatively activated M2 ATMs. Persistent or frequent consumption of calorie-dense food results in obesity that is associated with increased adiposity which includes adipose tissue hypertrophy and influx of proinflammatory monocytes that mature to classically activated M1 ATMs. Obesity induces production of proinflammatory cytokines (i.e., IL-6, TNF , and IL-1 ) and several chemokines including CCL2, CCL5, and CXCL5 among others by adipocytes and immune cells trigger adipose tissue inflammation, which when prolonged progresses to systemic inflammation that affects (i) vasculature increasing permeability of endothelium, thereby triggering plaque development and cardiovascular disease; (ii) anabolic actions of insulin and insulin signaling in metabolic tissues including liver and skeletal muscle, causing insulin resistance that manifests as impaired glucose disposal in muscle and altered cholesterol and glucose metabolism in the liver, which in turn triggers hyperinsulinemia, hyperglycemia, and hyperlipidemia that all contribute to type 2 diabetes and cardiovascular disease; and (iii) pancreas, decreasing insulin secretion that leads to hyperglycemia, which is a hallmark of diabetes.
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