Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity
- Nagareddy, PR; Kraakman, M; Masters, SL; Stirzaker, RA; Gorman, DJ; Grant, RW; Dragoljevic, D; Hong, ES; Abdel-Latif, A; Smyth, SS; Choi, SH; Korner, J; Bornfeldt, KE; Fisher, EA; Dixit, VD; Tall, AR; Goldberg, IJ; Murphy, AJ;
Publication Year 2014-05-06, Volume 19, Issue #5, Page 821-35
- Journal Title
- Cell Metab
- Publication Type
- Journal Article
- 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-1beta production. IL-1beta 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-1beta signaling axis could reduce AT inflammation and insulin resistance in obesity.
- Cell Press
- WEHI Research Division(s)
- Publisher's Version
- https://doi.org/S1550-4131(14)00163-6 [pii]; 10.1016/j.cmet.2014.03.029 [doi]
- Rights Notice
- Copyright © 2014 Elsevier Inc. All rights reserved.
Creation Date: 2014-05-20 08:08:54Last Modified: 0001-01-01 12:00:00