Iron homeostasis: a new job for macrophages in adipose tissue?

• Studies have linked elevated body iron stores to obesity and metabolic syndrome in humans.
• Iron levels in adipose tissue are important for adipogenesis and adipocyte function.
• Iron-enriched macrophages in adipose tissue have an iron-cycling profile, increased Hmox1 expression, and their phenotype is altered in obesity.
• In obesity, adipocytes become iron-overloaded concomitant with reduced macrophage iron content.

Elevated serum ferritin and increased cellular iron concentrations are risk factors for diabetes; however, the etiology of this association is unclear. Metabolic tissues such as pancreas, liver, and adipose tissue (AT), as well as the immune cells resident in these tissues, may be involved. Recent studies demonstrate that the polarization status of macrophages has important relevance to their iron-handling capabilities. Furthermore, a subset of macrophages in AT have elevated iron concentrations and a gene expression profile indicative of iron handling, a capacity diminished in obesity. Because iron overload in adipocytes increases systemic insulin resistance, iron handling by AT macrophages may have relevance not only to adipocyte iron stores but also to local and systemic insulin sensitivity.