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

生长激素重塑炎性巨噬细胞线粒体的三维结构并促进代谢重编程

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作者:Blanca Soler Palacios, Ricardo Villares, Pilar Lucas, José Miguel Rodríguez-Frade, Ana Cayuela, Jonathan G Piccirillo, Manuel Lombardía, David Delgado Gestoso, Miguel Fernández-García, Cristina Risco, Coral Barbas, Fernando Corrales, Carlos Oscar S Sorzano, Nuria Martínez-Martín, José Javier Conesa,

Conclusions

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 as a new target to intervene in inflammatory diseases.

Methods

Here we use biochemical analysis, correlative cryogenic fluorescence microscopy and cryo-focused ion-beam scanning electron microscopy.

Results

We demonstrate that growth hormone (GH) reprograms inflammatory GM-CSF-primed monocyte-derived macrophages (GM-MØ) by functioning as a metabolic modulator. We found that exogenous treatment of GM-MØ with recombinant human GH reduced glycolysis and lactate production to levels similar to those found in anti-inflammatory M-MØ. Moreover, GH treatment of GM-MØ augmented mitochondrial volume and altered mitochondrial dynamics, including the remodeling of the inner membrane to increase the density of cristae. Conclusions: 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 as a new target to intervene in inflammatory diseases.

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