First Author | Zhang H | Year | 2017 |
Journal | Obesity (Silver Spring) | Volume | 25 |
Issue | 8 | Pages | 1410-1420 |
PubMed ID | 28650582 | Mgi Jnum | J:272132 |
Mgi Id | MGI:6282693 | Doi | 10.1002/oby.21900 |
Citation | Zhang H, et al. (2017) Synergistic Modulation of Inflammatory but not Metabolic Effects of High-Fat Feeding by CCR2 and CX3CR1. Obesity (Silver Spring) 25(8):1410-1420 |
abstractText | 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. |