Linking resistin, inflammation, and cardiometabolic diseases

Abstract

Adipose tissue secretes a variety of bioactive substances that are associated with chronic inflammation, insulin resistance, and an increased risk of type 2 diabetes mellitus. While resistin was first known as an adipocyte-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents, it is predominantly expressed and secreted by macrophages in humans. Epidemiological and genetic studies indicate that increased resistin levels are associated with the development of insulin resistance, diabetes, and cardiovascular disease. Resistin also appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and the formation of foam cells. Thus, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with cardiovascular disease and heart failure. Furthermore, recent evidence suggests that resistin is associated with atherogenic dyslipidemia and hypertension. The present review will focus on the role of human resistin in the pathogeneses of inflammation and obesity-related diseases.

Resistin is a prognostic factor for death in type 2 diabetes

“…Human resistin also upregulates intercellular adhesion molecule‐1 (ICAM‐1) and endothelial adhesion molecules, including vascular cell‐adhesion molecule‐1 (VCAM‐1), involved in leukocyte chemotaxis to sites of inflammation . By triggering subclinical inflammation, resistin promotes endothelial dysfunction and atherosclerosis . Resistin appears to be involved in the development of atherosclerotic plaque also by inducing vascular smooth muscle cell proliferation and formation of foam cells .…”

“…However, these presumptions were based largely on the results of experiments in rodent models, and subsequent studies have yielded a hypothesis that human resistin should be considered primarily an inflammatory marker . Resistin is released not only from adipocytes but also (and mainly) from peripheral‐blood mononuclear cells and macrophages in response to lipopolysaccharides and pro‐inflammatory cytokines . In turn, human resistin increases the expression of TNF‐α and interleukins 1, 6, and 12 .…”

“…19,20 Resistin is released not only from adipocytes but also (and mainly) from peripheral-blood mononuclear cells and macrophages in response to lipopolysaccharides and pro-inflammatory cytokines. 21,22 In turn, human resistin increases the expression of TNF-α and interleukins 1, 6, and 12. 22,23 Serum resistin concentrations have been shown to correlate with TNF-α levels.…”

“…23 By triggering subclinical inflammation, resistin promotes endothelial dysfunction and atherosclerosis. 21,22 Resistin appears to be involved in the development of atherosclerotic plaque also by inducing vascular smooth muscle cell proliferation and formation of foam cells. 22,25,26 Still, in some (although not all) studies, higher-resistin concentrations were reported in obese or T2D patients compared with controls.…”

Ascitic fluid regulates the local innate immune response of patients with cirrhosis

“…Resistin was first identified as an adipocyte‐secreted hormone in rodents, but it was almost undetectable in human adipose tissue and highly expressed in circulating leukocytes and bone marrow. We detected resistin secretion by neutrophils, but not by monocytes, and this secretion increased upon activation. In line with our findings, resistin has been shown to be secreted by circulating neutrophils in patients with Graves’ disease and sepsis …”