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Macrophage depletion results in anemia, neutrophilia, and is not an effective therapy for rescuing obesity-linked metabolic impairments
Low-grade, chronic inflammation is thought to play a role in obesity-associated metabolic dysfunction. In obesity, macrophages account for approximately 50% of adipose tissue cells and can secrete a variety of proinflammatory cytokines. In this study, we sought to deplete macrophages in order to dec...
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Published in: | The Journal of immunology (1950) 2018-05, Vol.200 (1_Supplement), p.42-42.20 |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | Low-grade, chronic inflammation is thought to play a role in obesity-associated metabolic dysfunction. In obesity, macrophages account for approximately 50% of adipose tissue cells and can secrete a variety of proinflammatory cytokines. In this study, we sought to deplete macrophages in order to decrease macrophage-mediated inflammation and rescue metabolic dysfunction. Following 16 weeks of high-fat diet (HFD) (40% of total kcal from fat) or AIN-76A control diet consumption (n=30), male C57BL/6J mice within each diet cohort were assigned to either a clodronate (CLD)-liposome or PBS-liposome-treatment (n=15/group). Mice received 200 μl (1mg) i.p. injections of CLD or PBS-encapsulated liposomes (control group) twice weekly for 4 weeks to deplete macrophages. Metabolic function was assessed via the HOMA-IR, glucose and insulin tolerance tests, and serum free fatty acids. Adipose tissue, liver, and blood were analyzed for macrophage infiltration, inflammatory mediators and circulating cell populations. HFD-fed mice exhibited an obese phenotype compared to the control diet; however, macrophage depletion was unable to rescue metabolic dysfunction. Interestingly, macrophage-depleted mice had >35% increase in circulating neutrophils and adipose tissue Ly6G content. The increase in neutrophils, likely a compensation for the depletion of macrophages, was linked to an increase in the proinflammatory cytokines, IL-6 and IL1β, in the adipose tissue. Additionally, the decrease in macrophages resulted in iron-deficient anemia. Our study suggests that depleting macrophages in an obese setting is not an effective therapy for rescuing metabolic dysfunction and may increase the risk for anemia and adipose tissue inflammation. |
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ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.200.Supp.42.20 |