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Adipose tissue biology

Iron at the intersection of macrophage–adipocyte interactions

Nature Metabolism volume 4, pages 1434–1435 (2022)Cite this article

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Scherer and colleagues demonstrate that manipulation of iron concentrations in the mitochondrial matrix of macrophages has profound effects on their polarization, leading to concomitant changes in adipocyte iron concentrations and, ultimately, systemic metabolic effects.

Iron is essential to life and to the function of all cells. Most iron in the body is found circulating in the blood within red blood cells (in hemoglobin) or stored in muscle (in myoglobin). Because free iron is toxic, it is efficiently bound by transferrin and can be transported within the blood for tissue uptake. There are many functions of iron within the body, including in oxygen delivery, as a cofactor for various enzymes, in DNA synthesis and in mitochondrial electron transport chain activity. Iron concentrations within the body are regulated at two main sites: absorption by enterocytes in the gut and recycling of senescent red blood cells by macrophages in the spleen. Systemically, iron concentrations are regulated to support erythropoiesis and to inhibit bacterial growth. Increased iron concentrations in metabolic organs such as the pancreas, liver and adipose tissue have been shown to increase risk of diabetes and other metabolic diseases1. Thus, understanding iron regulation at the tissue level is critical to defining the contribution of iron to chronic diseases. Emerging evidence suggests that tissue-resident macrophages regulate iron concentrations at the local level; we have previously referred to them as ‘ferrostats’2. A new study now shows that mitochondrial iron content in macrophages has a marked impact on macrophage polarization, adipocyte iron concentrations and systemic metabolic homeostasis3.

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Fig. 1: Iron is part of the macrophage–adipocyte paracrine loop.

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Acknowledgements

A.H.H. is supported the National Institute of Diabetes and Digestive and Kidney Diseases (grant no. DK121520) and by a Career Scientist Award from the Veterans Affairs (grant no. IK6 BX005649).

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  1. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA

    Alyssa H. Hasty

  2. VA Tennessee Valley Healthcare System, Nashville, TN, USA

    Alyssa H. Hasty

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Correspondence to Alyssa H. Hasty.

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Hasty, A.H. Iron at the intersection of macrophage–adipocyte interactions. Nat Metab 4, 1434–1435 (2022). https://doi.org/10.1038/s42255-022-00663-0

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