Department of Molecular Physiology and Biophysics, School of Medicine, Vanderbilt University , Nashville, Tennessee.
Department of Nutrition, University of North Carolina at Greensboro , Greensboro, North Carolina.
Am J Physiol Cell Physiol. 2018 Sep 1;315(3):C319-C329. doi: 10.1152/ajpcell.00103.2018. Epub 2018 May 16.
Resident adipose tissue macrophages (ATMs) play multiple roles to maintain tissue homeostasis, such as removing excess free fatty acids and regulation of the extracellular matrix. The phagocytic nature and oxidative resiliency of macrophages not only allows them to function as innate immune cells but also to respond to specific tissue needs, such as iron homeostasis. MFe ATMs are a subtype of resident ATMs that we recently identified to have twice the intracellular iron content as other ATMs and elevated expression of iron-handling genes. Although studies have demonstrated that iron homeostasis is important for adipocyte health, little is known about how MFe ATMs may respond to and influence adipose tissue iron availability. Two methodologies were used to address this question: dietary iron supplementation and intraperitoneal iron injection. Upon exposure to high dietary iron, MFe ATMs accumulated excess iron, whereas the iron content of MFe ATMs and adipocytes remained unchanged. In this model of chronic iron excess, MFe ATMs exhibited increased expression of genes involved in iron storage. In the injection model, MFe ATMs incorporated high levels of iron, and adipocytes were spared iron overload. This acute model of iron overload was associated with increased numbers of MFe ATMs; 17% could be attributed to monocyte recruitment and 83% to MFe ATM incorporation into the MFe pool. The MFe ATM population maintained its low inflammatory profile and iron-cycling expression profile. These studies expand the field's understanding of ATMs and confirm that they can respond as a tissue iron sink in models of iron overload.
驻留于脂肪组织的巨噬细胞（ATMs）在维持组织内环境稳态方面发挥着多种作用，例如清除多余的游离脂肪酸和调节细胞外基质。巨噬细胞的吞噬特性和抗氧化弹性不仅使它们能够作为先天免疫细胞发挥作用，而且还能响应特定的组织需求，如铁稳态。MFe ATMs 是我们最近发现的一种驻留 ATMs 亚型，其细胞内铁含量是其他 ATMs 的两倍，并且铁处理基因的表达水平升高。尽管研究表明铁稳态对脂肪细胞健康很重要，但对于 MFe ATMs 如何响应和影响脂肪组织铁的可用性知之甚少。我们使用了两种方法来解决这个问题：饮食中铁的补充和腹腔内铁注射。暴露于高膳食铁后，MFe ATMs 积累了过量的铁，而 MFe ATMs 和脂肪细胞的铁含量保持不变。在这个慢性铁过量的模型中，MFe ATMs 表达参与铁储存的基因增加。在注射模型中，MFe ATMs 摄取了高水平的铁，而脂肪细胞则免受铁过载的影响。这种急性铁过载模型与 MFe ATMs 数量的增加有关；其中 17%可归因于单核细胞募集，83%归因于 MFe ATM 纳入 MFe 池。MFe ATM 群体保持其低炎症特征和铁循环表达特征。这些研究扩展了人们对 ATMs 的理解，并证实它们可以作为铁过载模型中的组织铁库进行响应。
