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Synergistic Modulation of Inflammatory but not Metabolic Effects of High‐Fat Feeding by CCR2 and CX3CR1
Author(s) -
Zhang Hanrui,
Hinkle Christine C,
O'Neill Sean M.,
Shi Jianting,
Caughey Jennifer,
Lynch Emma,
Lynch Gina,
Gerelus Mark,
Tsai Andrew S. D.,
Shah Rachana,
Ferguson Jane F.,
Ahima Rexford S.,
Reilly Muredach P.
Publication year - 2017
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.21900
Subject(s) - cx3cr1 , ccr2 , adipose tissue , medicine , endocrinology , chemokine , knockout mouse , chemokine receptor , cd11c , inflammation , receptor , phenotype , biology , biochemistry , gene
Objective The purpose of the study was to explore the impact of dual targeting of C‐C motif chemokine receptor‐2 (CCR2) and fractalkine receptor (CX3CR1) on the metabolic and inflammatory consequences of obesity induced by a high‐fat diet (HFD). Methods C57BL/6J wild‐type, Cx3cr1 −/− , Ccr2 −/− , and Cx3cr1 −/− Ccr2 −/− double‐knockout male and female mice were fed a 45% HFD for up to 25 weeks starting at 12 weeks of age. Results All groups gained weight at a similar rate and developed a similar degree of adiposity, hyperglycemia, glucose intolerance, and impairment of insulin sensitivity in response to HFD. As expected, the circulating monocyte count was decreased in Ccr2 −/− and Cx3cr1 −/− Ccr2 −/− mice but not in Cx3cr1 −/− mice. Flow cytometric analysis of perigonadal adipose tissue of male, but not female, mice revealed trends to lower CD11c+MGL1− M1‐like macrophages and higher CD11c−MGL1+ M2‐like macrophages as a percentage of CD45+F4/80+CD11b+ macrophages in Cx3cr1 −/− Ccr2 −/− mice versus wild‐type mice, suggesting reduced adipose tissue macrophage activation. In contrast, single knockout of Ccr2 or Cx3cr1 did not differ in their adipose macrophage phenotypes. Conclusions Although CCR2 and CX3CR1 may synergistically impact inflammatory phenotypes, their joint deficiency did not influence the metabolic effects of a 45% HFD‐induced obesity in these model conditions.