Abstract
Obesity is associated with a state of chronic low-grade inflammation both systemically and within specific tissues, including adipose tissue (AT). In murine models of obesity, there is a shift in the inflammatory profile of the AT immune cells, with an accumulation of proinflammatory M1 macrophages that surround the expanding adipocyte. However, much less is known about the immune cell composition and how to best define AT macrophages in humans. Objective. The goals of the current study were to determine the contribution of macrophages to the stromal vascular fraction (SVF) in lean versus obese human visceral AT (VAT); examine the expression of common M1, M2, and pan macrophage markers; and determine the association of specific macrophage types with known biomarkers of obesity-related cardiometabolic disease. Research Design and Methods. VAT biopsies were obtained from obese (n = 50) and lean (n = 8) patients during elective surgery. Adipocytes and SVF were isolated, and the SVF was subjected to flow cytometry analyses. Results. Our results indicate that VAT macrophages are increased in obesity and associate with biomarkers of CVD but that many macrophages do not fall into currently defined M1/M2 classification system based on CD206 receptor expression levels. Conclusions. VAT macrophages are increased in obese subjects, but the current markers used to define macrophage populations are inadequate to distinguish differences in human obesity. Further studies are needed to delineate the function of AT macrophages in the maintenance and progression of human AT inflammation in obesity.
Highlights
The prevalence of obesity has risen to epidemic proportions in the last decade, affecting greater than 30% of adults in the United States [1]
Body mass index (BMI), as well as multiple metabolic parameters including the presence of diabetes, insulin resistance (HOMA-IR), and fasting insulin, was significantly higher in obese compared to lean patients
Patterns of cluster of differentiation (CD)206 expression were similar between both groups, with roughly 30% of adipose tissue (AT) macrophages expressing high levels of CD206 and around 60% expressing low levels of CD206 (Figure 1). These results indicate that classifying macrophages by CD206 does not adequately distinguish differences in the AT macrophage population observed in lean compared to obese humans
Summary
The prevalence of obesity has risen to epidemic proportions in the last decade, affecting greater than 30% of adults in the United States [1]. In accordance with this increase, there has been a proportional rise in the incidence of obesityrelated comorbidities, including type 2 diabetes mellitus (T2DM), atherosclerosis, heart disease, and stroke [2]. One of the primary immune cells, the macrophage, is characterized as a M1, proinflammatory CD11c-expressing macrophage, or a M2, anti-inflammatory CD206-expressing macrophage [9]. The SVF in lean mice is composed of primarily anti-inflammatory immune cells
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