biostudies-literatureUnknownMelika ET<h4>Background</h4>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.<h4>Methods</h4>Male C57BL/6J mice were injected intravenously with hepatotropic adeno-associated virus (AAV2/8) carrying <i>Ifng</i> and <i>nLuc</i> reporter under the albumin promoter (AAV-<i>Ifng</i>) or empty vector control virus (AAV-ctrl). Cardiac alterations were monitored on day 28 through flow cytometry, bulk RNA sequencing, targeted metabolomics, isolated mitochondrial activity, echocardiography, and in vivo imbioRxiv : the preprint server for biology2025.08.31.673391https://www.ebi.ac.uk/biostudies/studies/S-EPMC12424622biostudies-literatureInterferon gamma signaling drives cardiac metabolic rewiring.PMC12424622Kuhn MHofmann UVath MKarlstaedt ANickel AKim KArampatzi PMelika ETHiguchi TFrantz SMaack CRamos GCArias-Loza PGasteiger GSrivastava MChen XCunha EAshour DfalseInterferon gamma signaling drives cardiac metabolic rewiring.<h4>Background</h4>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.<h4>Methods</h4>Male C57BL/6J mice were injected intravenously with hepatotropic adeno-associated virus (AAV2/8) carrying <i>Ifng</i> and <i>nLuc</i> reporter under the albumin promoter (AAV-<i>Ifng</i>) or empty vector control virus (AAV-ctrl). Cardiac alterations were monitored on day 28 through flow cytometry, bulk RNA sequencing, targeted metabolomics, isolated mitochondrial activity, echocardiography, and in vivo im2025-01-01T00:00:00Z2025 Sep2026-05-26T20:05:58.759Z2026-05-26T03:06:36.7ZS-EPMC124246224095009910.1101/2025.08.31.673391