ArticlebioRxiv : the preprint server for biology2025
Interferon gamma signaling drives cardiac metabolic rewiring.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: IFN-gamma (IFN-γ) signaling influences myocardial inflammation and fibrosis across a wide range of conditions, including ischemic and non-ischemic heart failure (HF). However, the direct effects of IFN-γ on cardiomyocytes remain poorly understood. Here, we developed a novel in vivo model to investigate how IFN-γ impacts myocardial metabolism and function. Methods: Male C57BL/6J mice were injected intravenously with hepatotropic adeno-associated virus (AAV2/8) carrying Results: After confirming liver-specific viral transfection and elevated serum IFN-γ production at physiological levels, we observed cardiac metabolic adaptation and rewiring in animals treated with AAV- Conclusions: Systemic IFN-γ induces pronounced metabolic reprogramming in the heart, characterized by increased glucose uptake and reduced oxidative phosphorylation, via direct signaling through cardiomyocyte IFNGR. These alterations mirror those observed in aging and some forms of HF, thereby highlighting that, beyond classical inflammation, this cytokine regulates cardiac metabolism.
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