Remodeling Phenotype of Human Subcutaneous Adipose Tissue Macrophages

Abstract

Background-Adipose tissue macrophages (ATMs) have become a focus of attention recently because they have been shown to accumulate with an increase in fat mass and to be involved in the genesis of insulin resistance in obese mice. However, the phenotype and functions of human ATMs are still to be defined. Methods and Results-The present study, performed on human subcutaneous AT, showed that ATMs from lean to overweight individuals are composed of distinct macrophage subsets based on the expression of several cell surface markers: CD45, CD14, CD31, CD44, HLA-DR, CD206, and CD16, as assessed by flow cytometry. ATMs isolated by an immunoselection protocol showed a mixed expression of proinflammatory (tumor necrosis factor-␣, interleukin-6 [IL-6], IL-23, monocyte chemoattractant protein-1, IL-8, cyclooxygenase-2) and antiinflammatory (IL-10, transforming growth factor-␤, alternative macrophage activation-associated cc chemokine-1, cyclooxygenase-1) factors. Fat mass enlargement is associated with accumulation of the CD206 ϩ /CD16 Ϫ macrophage subset that exhibits an M2 remodeling phenotype characterized by decreased expression of proinflammatory IL-8 and cyclooxygenase-2 and increased expression of lymphatic vessel endothelial hyaluronan receptor-1. ATMs specifically produced and released matrix metalloproteinase-9 compared with adipocytes and capillary endothelial cells, and secretion of matrix metalloproteinase-9 from human AT in vivo, assessed by arteriovenous difference measurement, was correlated with body mass index. Finally, ATMs exerted a marked proangiogenic effect on AT-derived endothelial and progenitor cells. Conclusions-The present results showed that the ATMs that accumulate with fat mass development exhibit a particular M2 remodeling phenotype. ATMs may be active players in the process of AT development through the extension of the capillary network and in the genesis of obesity-associated cardiovascular pathologies.

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

“…In contrast, adipose tissue macrophages may also have cytoprotective anti-inflammatory properties, as identified by the expression of several markers that determine an alternatively activated, anti-inflammatory macrophage type, 12,13 for instance, the hemoglobin scavenger receptor CD163. 10,14 CD163 is exclusively expressed on monocytes and macrophages and mediates endocytosis of haptoglobinhemoglobin complexes, 15 thereby preventing oxidative and nitrosative toxicity emerging upon red blood cell hemolysis. 16 Moreover, CD163-mediated uptake of hemoglobin into the macrophage fuels an anti-inflammatory response driven by heme oxygenase-1 activity, leading to potent anti-inflammatory heme metabolites.…”

Soluble CD163: a biomarker linking macrophages and insulin resistance

“…Different phenotypes have been described that do not fit simple categories of pro-or anti-inflammatory macrophages, but are characterised by excretion of inflammatory cytokines such as TNF-α and IL-6 [3,23,24]. These cytokines induce insulin resistance in the liver, which in turn stimulates the production of CRP [25].…”

Increased Epicardial, Pericardial, and Subcutaneous Adipose Tissue Is Associated with the Presence and Severity of Coronary Artery Calcium

“…Bourlier et al (28) reported that adipose tissue macrophages in subcutaneous fat depot are composed of distinct macrophage subsets from lean to overweight individuals. These adipose tissue macrophages are active players in the process of adipose tissue development by extending capillary network, genesis of obesity-associated pathologies, systemic inflammation, insulin resistance, and endotoxemia (28).…”

“…These adipose tissue macrophages are active players in the process of adipose tissue development by extending capillary network, genesis of obesity-associated pathologies, systemic inflammation, insulin resistance, and endotoxemia (28).…”