Adipose tissue macrophages (ATMs) accumulate in fat during obesity and resemble foam cells in atherosclerotic lesions, suggesting that common mechanisms underlie both inflammatory conditions. CX 3 CR1 and its ligand fractalkine/CX 3 CL1 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 CX 3 CR1 regulates ATM trafficking to epididymal fat and contributes to the development of adipose tissue inflammation during diet-induced obesity. CX 3cl1 and CX 3 expression was induced specifically in epididymal fat from mice fed a high-fat diet (HFD). CX 3 CR1 was detected on multiple myeloid cells within epididymal fat from obese mice. To test the requirement of CX 3 CR1 for ATM trafficking and obesity-induced inflammation, CX 3 cr1 +GFP and CX 3 cr1 GFP/GFP mice were fed a HFD. Ly-6c Low monocytes were reduced in lean CX 3cr1 GFP/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 CX 3 cr1 +GFP and CX 3 cr1 GFP/GFP mice. CX 3 cr1 deficiency did not prevent the development of obesity-induced insulin resistance or hepatic steatosis. In summary, our data indicate that CX 3 CR1 is not required for the recruitment or retention of ATMs in epididymal adipose tissue of mice with HFD-induced obesity even though CX 3 CR1 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.
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Endocrinology, Diabetes and Metabolism
- Nutrition and Dietetics