CX₃CR1 Deficiency Does Not Influence Trafficking of Adipose Tissue Macrophages in Mice With Diet‐Induced Obesity

Abstract

Adipose tissue macrophages (ATMs) accumulate in fat during obesity and resemble foam cells in atherosclerotic lesions, suggesting that common mechanisms underlie both inflammatory conditions. CX3CR1 and its ligand fractalkine/CX3CL1 contribute to macrophage recruitment and inflammation in atherosclerosis, but their role in obesity-induced adipose tissue inflammation is unknown. Therefore, we tested the hypothesis that CX3CR1 regulates ATM trafficking to epididymal fat and contributes to the development of adipose tissue inflammation during diet-induced obesity. Cx3cl1 and Cx3cr1 expression was induced specifically in epididymal fat from mice fed a high-fat diet (HFD). CX3CR1 was detected on multiple myeloid cells within epididymal fat from obese mice. To test the requirement of CX3CR1 for ATM trafficking and obesity-induced inflammation, Cx3cr1+/GFP and Cx3cr1GFP/GFP mice were fed a HFD. Ly-6cLow monocytes were reduced in lean Cx3cr1GFP/GFP mice; however, HFD-induced monocytosis was comparable between strains. Total ATM content, the ratio of type 1 (CD11c+) to type 2 (CD206+) ATMs, expression of inflammatory markers, and T-cell content were similar in epididymal fat from obese Cx3cr1+/GFP and Cx3cr1GFP/GFP mice. Cx3cr1 deficiency did not prevent the development of obesity-induced insulin resistance or hepatic steatosis. In summary, our data indicate that CX3CR1 is not required for the recruitment or retention of ATMs in epididymal adipose tissue of mice with HFD-induced obesity even though CX3CR1 promotes foam cell formation. This highlights an important point of divergence between the mechanisms regulating monocyte trafficking to fat with obesity and those that contribute to foam cell formation in atherogenesis.

Adipose tissue macrophages in non-rodent mammals: a comparative study

“…S1). This finding was in accordance with previous studies showing that this cell population is rich in ATMs (Morris et al 2012). The Type B population was lacking F4/80 and Mac-3/Lamp-2 expression (Fig.…”

“…S1). This accords with a previous finding that this cell population contains immature myeloid cells (Morris et al 2012). In all species, the Type A population contained larger cells than the Type B population, as shown by their higher FSC-A values (Figs.…”

The fractalkine/Cx3CR1 system is implicated in the development of metabolic visceral adipose tissue inflammation in obesity

“…Our results on diet-induced obesity in Cx3CR1 gfp mice differ from other reports on this model. For instance, Morris et al [26] and Lee et al [27] failed to detect differences in HFD induced body weight and adiposity in fractalkine receptor KO mice and controls. These discrepancies might be due to different fat composition (60% fat for Morris vs.…”

Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo

“…The CX 3 CR1 GFP mouse has been widely used as the transgenic of choice to investigate monocyte recruitment and trafficking. 11,31,32 In this study, we carried out a side-by-side comparative analysis of CX 3 CR1…”