2. Academic Validation
  3. cTnIR193H restrictive cardiomyopathy mice satisfy high-energy metabolic demands through regulating glucose metabolism

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

  • Genes Dis. 2025 Jul 25;13(2):101784. doi: 10.1016/j.gendis.2025.101784.
Min Luo 1 2 3 4 5 6,  Lingjuan Liu 1 2 3 4 5 6,  Wenjing Yuan 1 2 3 4 5 6,  Junjun Quan 1 2 3 4 5 6,  Mi Li 1 2 3 4 5 6,  Jie Tian 1 2 3 4 5 6
Affiliations

Affiliations

  • 1 Department of Cardiology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
  • 2 National Clinical Research Center for Child Health and Disorders, Chongqing 400014, China.
  • 3 Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China.
  • 4 Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing 400014, China.
  • 5 National Clinical Key Cardiovascular Specialty, Chongqing 400014, China.
  • 6 Key Laboratory of Children's Important Organ Development and Diseases of Chongqing Municipal Health Commission, Chongqing 400014, China.
PMID: 41445980 DOI: 10.1016/j.gendis.2025.101784
Abstract

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.

Keywords

Glucose and fatty acid intake; Glucose metabolism; PI3K/Akt; Restrictive cardiomyopathy; cTnIR193H mutation.

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