Resistin in rodents and humans

Abstract

Obesity is characterized by excess accumulation of lipids in adipose tissue and other organs, and chronic inflammation associated with insulin resistance and an increased risk of type 2 diabetes. Obesity, type 2 diabetes, and cardiovascular diseases are major health concerns. Resistin was first discovered as an adipose-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents. Adipocyte-derived resistin is increased in obese rodents and strongly related to insulin resistance. However, in contrast to rodents, resistin is expressed and secreted from macrophages in humans and is increased in inflammatory conditions. Some studies have also suggested an association between increased resistin levels and insulin resistance, diabetes and cardiovascular disease. Genetic studies have provided additional evidence for a role of resistin in insulin resistance and inflammation. Resistin appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and formation of foam cells. Indeed, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. There is also growing evidence that elevated resistin is associated with the development of heart failure. This review will focus on the biology of resistin in rodents and humans, and evidence linking resistin with type 2 diabetes, atherosclerosis, and cardiovascular disease.

Keywords: Adipocytes; Atherosclerosis; Cardiovascular diseases; Diabetes mellitus, type 2; Inflammation; Insulin resistance; Macrophages; Obesity; Polymorphism, genetic; Resistin.

Fig. 1

Roles of resistin in inflammation, glucose homeostasis, and cardiovascular diseases. Resistin is induced in response to various stimuli, including proinflammatory cytokines, lipopolysaccharide (LPS), and genetically determined factors. Resistin targets several types of cells, promoting inflammation, insulin resistance, and atherosclerosis. Resistin is up-regulated and secreted from PBMC and macrophages, and in turn, acts on these cells, leading to the development of insulin resistance and enhancing inflammatory processes through activation of nuclear factor (NF)-κB. Resistin contributes to the pathogenesis of atherosclerosis by disrupting vascular endothelial cellular function, and increasing proliferation of smooth muscle cells, and foam cell transformation. Resistin directly affects the function of cardiomyocytes predisposing to myocardial injury. Adapted from Schwartz et al. Trends Endocrinol Metab 2011;22:259-65, with permission from Elsevier [55]. HSC, hepatic stellate cell; MCP, monocyte chemoattractant protein; IL, interleukin; TNF, tumor necrosis factor; PBMC, peripheral blood mononuclear cell; ICAM, intercellular adhesion molecule; VCAM, vascular cell adhesion molecule; ET, endothelin; VSMC, vascular smooth muscle cell; ERK, extracellular signal-regulated kinase; PI3K, phosphatidylinositol-3-kinase; MAPK, mitogen-activated protein kinase; TZD, thiazolidinedione.