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Cell Metab. 2014 May 6;19(5):821-35. doi: 10.1016/j.cmet.2014.03.029.

Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity.

Author information

  • 1Division of Preventive Medicine and Nutrition, Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Internal Medicine, University of Kentucky, Lexington, KY 40514, USA.
  • 2Haematopoiesis and Leukocyte Biology, Baker IDI Heart and Diabetes Institute, Melbourne VIC 3004, Australia.
  • 3Division of Inflammation, Walter and Eliza Hall Institute of Medical Research, Melbourne VIC 3052, Australia.
  • 4Division of Preventive Medicine and Nutrition, Department of Medicine, Columbia University, New York, NY 10032, USA.
  • 5Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA.
  • 6Pennington Biomedical Research Institute, Louisiana State University, Baton Rouge, LA 70803, USA.
  • 7Department of Medicine, Seoul National University, Seoul 151-742, South Korea.
  • 8Department of Internal Medicine, University of Kentucky, Lexington, KY 40514, USA.
  • 9Division of Endocrinology, Department of Medicine, Columbia University, New York, NY 10032, USA.
  • 10Department of Medicine and Department of Pathology, University of Washington, Seattle, WA 98109, USA.
  • 11Division of Cardiology, New York University School of Medicine, New York, NY 10016, USA.
  • 12Pennington Biomedical Research Institute, Louisiana State University, Baton Rouge, LA 70803, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 13Division of Preventive Medicine and Nutrition, Department of Medicine, Columbia University, New York, NY 10032, USA; Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine, New York, NY 10016, USA.
  • 14Haematopoiesis and Leukocyte Biology, Baker IDI Heart and Diabetes Institute, Melbourne VIC 3004, Australia; Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Immunology, Monash University, Melbourne VIC 3004, Australia. Electronic address: andrew.murphy@bakeridi.edu.au.

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.

Copyright © 2014 Elsevier Inc. All rights reserved.

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PMID:
24807222
[PubMed - indexed for MEDLINE]
PMCID:
PMC4048939
[Available on 2015-05-06]

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