Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity

Prabhakara Reddy Nagareddy, Michael J Kraakman, Seth L Masters, Roslynn A Stirzaker, Darren J Gorman, Ryan W Grant, Dragana Dragoljevic, Eun Shil Hong, Ahmed Abdel-Latif, Susan S Smyth, Sung Hee Choi, Judith Korner, Karin E Bornfeldt, Edward Allen Fisher, Vishwa Deep Dixit, Alan R Tall, Ira Jay Goldberg, Andrew James Murphy

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205 Citations (Scopus)

Abstract

Obesity is associated with infiltration of macrophages into adipose tissue (AT), contributing to insulin resistance and diabetes. However, relatively little is known regarding the origin of AT macrophages (ATMs). We discovered that murine models of obesity have prominent monocytosis and neutrophilia, associated with proliferation and expansion of bone marrow (BM) myeloid progenitors. AT transplantation conferred myeloid progenitor proliferation in lean recipients, while weight loss in both mice and humans (via gastric bypass) was associated with a reversal of monocytosis and neutrophilia. Adipose S100A8/A9 induced ATM TLR4/MyD88 and NLRP3 inflammasome-dependent IL-1? production. IL-1? interacted with the IL-1 receptor on BM myeloid progenitors to stimulate the production of monocytes and neutrophils. These studies uncover a positive feedback loop between ATMs and BM myeloid progenitors and suggest that inhibition of TLR4 ligands or the NLRP3-IL-1? signaling axis could reduce AT inflammation and insulin resistance in obesity.
Original languageEnglish
Pages (from-to)821 - 835
Number of pages15
JournalCell Metabolism
Volume19
Issue number5
DOIs
Publication statusPublished - 2014

Cite this

Nagareddy, P. R., Kraakman, M. J., Masters, S. L., Stirzaker, R. A., Gorman, D. J., Grant, R. W., Dragoljevic, D., Hong, E. S., Abdel-Latif, A., Smyth, S. S., Choi, S. H., Korner, J., Bornfeldt, K. E., Fisher, E. A., Dixit, V. D., Tall, A. R., Goldberg, I. J., & Murphy, A. J. (2014). Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity. Cell Metabolism, 19(5), 821 - 835. https://doi.org/10.1016/j.cmet.2014.03.029