Obesity Alters Adipose Tissue Macrophage Iron Content and Tissue Iron Distribution
- Jeb S. Orr1,
- Arion Kennedy1,
- Emily K. Anderson-Baucum1,
- Corey D. Webb1,
- Steve C. Fordahl2,
- Keith M. Erikson2,
- Yaofang Zhang3,
- Anders Etzerodt4,
- Søren K. Moestrup4 and
- Alyssa H. Hasty1⇑
- 1Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN
- 2Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC
- 3Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN
- 4Department of Biomedicine, Aarhus University, Aarhus, Denmark
- Corresponding author: Alyssa H. Hasty, .
Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, little is known regarding the role of alternatively activated resident M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we report the discovery of a population of alternatively activated ATMs with elevated cellular iron content and an iron-recycling gene expression profile. These iron-rich ATMs are referred to as MFehi, and the remaining ATMs are referred to as MFelo. In lean mice, ~25% of the ATMs are MFehi; this percentage decreases in obesity owing to the recruitment of MFelo macrophages. Similar to MFelo cells, MFehi ATMs undergo an inflammatory shift in obesity. In vivo, obesity reduces the iron content of MFehi ATMs and the gene expression of iron importers as well as the iron exporter, ferroportin, suggesting an impaired ability to handle iron. In vitro, exposure of primary peritoneal macrophages to saturated fatty acids also alters iron metabolism gene expression. Finally, the impaired MFehi iron handling coincides with adipocyte iron overload in obese mice. In conclusion, in obesity, iron distribution is altered both at the cellular and tissue levels, with AT playing a predominant role in this change. An increased availability of fatty acids during obesity may contribute to the observed changes in MFehi ATM phenotype and their reduced capacity to handle iron.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0213/-/DC1.
- Received February 6, 2013.
- Accepted October 8, 2013.
- © 2014 by the American Diabetes Association.
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