Growth hormone remodels the 3D-structure of the mitochondria of inflammatory macrophages and promotes metabolic reprogramming

Macrophages are a heterogeneous population of innate immune cells that support tissue homeostasis through their involvement in tissue development and repair, and pathogen defense. Emerging data reveal that metabolism may control macrophage polarization and function and, conversely, phenotypic polarization may drive metabolic reprogramming. Here, using biochemical analysis, correlative cryogenic fluorescence microscopy and cryo-focused ion-beam scanning electron microscopy, we demonstrate that growth hormone (GH) functions as a metabolic modulator to reprogram inflammatory GM-CSF-primed monocyte-derived macrophages (GM-MO). We found that exogenous treatment of GM-MO with recombinant human GH suppressed glycolysis, lactate production and non-mitochondrial respiration, and enhanced mitochondrial oxidative phosphorylation. Likewise, GH treatment augmented mitochondrial volume and altered mitochondrial dynamics, including the remodeling of the inner membrane to increase the density of cristae. Our data demonstrate that GH likely serves a modulatory role in the metabolism of inflammatory macrophages and suggest that metabolic reprogramming of macrophages should be considered a new target to intervene in multiple inflammatory diseases.