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

Hanrui Zhang, Christine C. Hinkle, Sean M. O'Neill, Jianting Shi, Jennifer Caughey, Emma Lynch, Gina Lynch, Mark Gerelus, Andrew S.D. Tsai, Rachana Shah, Jane F. Ferguson, Rexford S Ahima, Muredach P. Reilly

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1410-1420
Number of pages11
JournalObesity
Volume25
Issue number8
DOIs
StatePublished - Aug 1 2017

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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    Zhang, H., Hinkle, C. C., O'Neill, S. M., Shi, J., Caughey, J., Lynch, E., Lynch, G., Gerelus, M., Tsai, A. S. D., Shah, R., Ferguson, J. F., Ahima, R. S., & Reilly, M. P. (2017). Synergistic Modulation of Inflammatory but not Metabolic Effects of High-Fat Feeding by CCR2 and CX3CR1. Obesity, 25(8), 1410-1420. https://doi.org/10.1002/oby.21900