Monocyte control of organismal energy homeostasis

Multicellular organisms rely on inter-organ communication networks to maintain vital parameters within a dynamic physiological range. Macrophages are central to this homeostatic control system, sensing deviations of those parameters and responding accordingly to support tissue function and organismal homeostasis. Here we demonstrate that dysregulation of iron metabolism in parenchyma cells, imposed by the deletion of ferritin H chain, is sensed by monocyte-derived macrophages. In response, macrophages support tissue function, energy metabolism and thermoregulation, as demonstrated in bone marrow chimeric and parabiotic mice. This salutary effect is contingent on a transcriptional program, controlled in macrophages by the transcription factor A mitochondria. This transcriptional response acts in a non-cell autonomous manner to support the mitochondria of parenchyma cells, irrespectively of mitochondrial transfer. In conclusion, monocyte-derived macrophages cross-regulate Fe and energy metabolism to support tissue function and organismal homeostasis. Overall design: Goal: to assess the transcriptomic landscape of FTH-competent vs FTH-deleted monocytes/macrophages in the liver, white adipose tissue and hearts upon global deletion (or not) of ferritin (FTH) in parenchymal cells (from bone marrow chimeras). Specifically, we performed pairwise comparisons of Fth-competent vs. Fth-deleted macrophages from tdTLysM?FthR26?/? vs. tdTLysMFthLysM?/??FthR26?/? chimeras, where FTH is deleted in non-hematopoietic tissues (parenchyma), respectively. In addition, we performed pairwise comparisons of Fth-competent macrophages from control tdTLysM?Fthfl/fl vs. tdTLysM?FthR26?/? chimeras.