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Obesity (Silver Spring). 2017 Aug;25(8):1410-1420. doi: 10.1002/oby.21900. Epub 2017 Jun 26.

Synergistic Modulation of Inflammatory but not Metabolic Effects of High-Fat Feeding by CCR2 and CX3CR1.

Author information

1
Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, New York, USA.
2
Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
3
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
4
Vanderbilt Translational and Clinical Cardiovascular Research Center, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
5
Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
6
Irving Institute for Clinical and Translational Research, Columbia University, New York, New York, USA.

Abstract

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.

PMID:
28650582
PMCID:
PMC5610963
DOI:
10.1002/oby.21900
[Indexed for MEDLINE]
Free PMC Article

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