Synergistic Modulation of Inflammatory but not Metabolic Effects of High-Fat Feeding by CCR2 and CX3CR1
| Autor: | Muredach P. Reilly, Rachana Shah, Christine C. Hinkle, Jane F. Ferguson, Hanrui Zhang, Mark Gerelus, Jennifer Caughey, Emma Lynch, Gina Lynch, Sean O’Neill, Rexford S. Ahima, Andrew Tsai, Jianting Shi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty CCR2 Chemokine animal diseases Endocrinology Diabetes and Metabolism Medicine (miscellaneous) Adipose tissue Inflammation 03 medical and health sciences Endocrinology Insulin resistance Internal medicine parasitic diseases CX3CR1 medicine Receptor 2. Zero hunger Nutrition and Dietetics biology Chemistry hemic and immune systems medicine.disease 030104 developmental biology biology.protein medicine.symptom Weight gain |
| Zdroj: | Obesity. 25:1410-1420 |
| ISSN: | 1930-7381 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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