cTnIR193H restrictive cardiomyopathy mice satisfy high-energy metabolic demands through regulating glucose metabolism.

This work aims to investigate the energy metabolism in mice with restrictive cardiomyopathy induced by cardiac troponin I (cTnI) R193H mutation. Echocardiography was used to monitor cardiac function. ATP content and ATPase activity were detected with relevant kits. The expression levels of GLUT4, FAT/CD36, and PI3K/AKT pathway proteins were detected. Proteomics and phosphorylation omics were used to analyze the differential expression and modification of cardiac proteins and related pathways, respectively. The utilization of cardiac energy substrates was investigated using relevant kits. The isovolumic relaxation time of 4-month-old cTnI193His-M mice was significantly prolonged (P < 0.01); Cardiac ATP content, ATPase activity, and mitochondrial number were significantly increased (P < 0.05, P < 0.01, and P < 0.01, respectively); GLUT4 expression level increased (P < 0.01); the expression level of CD36 decreased (P < 0.01). Proteomic results showed that the glycolytic/gluconeogenic pathway was up-regulated. Phosphorylation omics was enriched in the inositol phosphate metabolism pathway and PI3K/AKT pathway. In conclusion, at the early stage of diastolic dysfunction, cTnI193His-M mice may increase glucose uptake and metabolism through the PI3K/AKT pathway to satisfy the high energy demand, which may contribute to the development of myocardial fibrosis and heart failure.