Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity.
Authors 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
Submitted By Submitted Externally on 12/11/2014
Status Published
Journal Cell Metabolism
Year 2014
Date Published 5/6/2014
Volume : Pages 19 : 821 - 835
PubMed Reference 24807222
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-1ß production. IL-1ß 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-1ß signaling axis could reduce AT inflammation and
insulin resistance in obesity.

Investigators with authorship
Karin BornfeldtUniversity of Washington
Edward FisherNew York University School of Medicine
Ira GoldbergNew York University School of Medicine