Article

Newly identified adipose tissue macrophage populations in obesity with distinct chemokine and chemokine receptor expression.

Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University Vienna, Vienna, Austria.
International journal of obesity (2005) (impact factor: 4.34). 12/2010; 34(12):1684-94. DOI:10.1038/ijo.2010.103 pp.1684-94
Source: PubMed

ABSTRACT Infiltration by macrophages is a hallmark of obesity-related adipose tissue (AT) inflammation that is tightly linked to insulin resistance. Although CD11c+ AT macrophages (ATMs) have recently been shown to promote inflammation in obese mice, the knowledge on phenotype and function of different ATM populations is still very limited. This study aimed at identifying and characterizing ATM populations in obesity.
Isolation of ATM populations defined by CD11c and mannose receptor (MR) expression and analysis of gene expression in high-fat diet-induced obese mice.
Obesity provoked a shift from a predominant MR+CD11c⁻ population ('MR-ATM') to two MR⁻ populations, namely MR⁻CD11c+ ('CD11c-ATM') and MR⁻CD11c⁻ (double negative, 'DN-ATM'). Although CD11c-ATMs were of a clear inflammatory M1 phenotype, DN-ATMs expressed few inflammatory mediators and highly expressed genes for alternative activation (M2) markers involved in tissue repair, such as arginase and YM1. In contrast, MR-ATMs marginally expressed M1 and M2 markers but highly expressed chemokines, including Mcp-1 (Ccl2) and Mcp-3 (Ccl7). Both CD11c-ATMs and DN-ATMs, but not MR-ATM, highly expressed a panel of chemokine receptors (namely Ccr2, Ccr5, Ccr3 and Cx3cr1), whereas the expression of Ccr7 and Ccr9 was selective for CD11c-ATMs and DN-ATMs, respectively. Notably, stressed adipocytes upregulated various chemokines capable of attracting CD11c-ATM and DN-ATM.
This study identifies a novel ATM population with a putatively beneficial role in AT inflammation. This DN-ATM population could be attracted to the obese AT by similar chemokines such as inflammatory CD11c-ATM, on which only Ccr7 is uniquely expressed.

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Keywords

adipocytes upregulated various chemokines capable
 
ATM populations
 
CD11c-ATMs
 
characterizing ATM populations
 
clear inflammatory M1 phenotype
 
different ATM populations
 
DN-ATM population
 
double negative
 
genes
 
high-fat diet-induced obese mice
 
inflammatory CD11c-ATM
 
insulin resistance
 
M2 markers
 
mannose receptor
 
MR⁻ populations
 
novel ATM population
 
obese mice
 
obesity-related adipose tissue
 
predominant MR+CD11c⁻ population
 
similar chemokines