| Literature DB >> 24807222 |
Prabhakara R Nagareddy1, Michael Kraakman2, Seth L Masters3, Roslynn A Stirzaker4, Darren J Gorman5, Ryan W Grant6, Dragana Dragoljevic2, Eun Shil Hong7, Ahmed Abdel-Latif8, Susan S Smyth8, Sung Hee Choi7, Judith Korner9, Karin E Bornfeldt10, Edward A Fisher11, Vishwa Deep Dixit12, Alan R Tall5, Ira J Goldberg13, Andrew J Murphy14.
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-1β production. IL-1β 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-1β signaling axis could reduce AT inflammation and insulin resistance in obesity.Entities:
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Year: 2014 PMID： 24807222 PMCID： PMC4048939 DOI： 10.1016/j.cmet.2014.03.029
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287