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

Autor: 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.
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Obesity (Silver Spring, Md.)
ISSN: 1930-739X
1930-7381
Popis: Objective 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 high fat diet (HFD)-induced obesity. Methods C57BL/6J wild type (WT), 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 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−/−, but not in Cx3cr1−/− Mice. Flow cytometric analysis of perigonadal adipose 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 vs. WT mice, suggesting reduced adipose tissue macrophage activation. In contrast, single knockout of Ccr2 or Cx3cr1 did not differ in their adipose macrophage phenotypes. Conclusion Although CCR2 and CX3CR1 may synergistically impact inflammatory phenotypes, their joint deficiency did not influence metabolic effects of 45% HFD-induced obesity in these model conditions.
Databáze: OpenAIRE
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