Related Experiment Video
Updated: Aug 10, 2026
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Integrated Multi-Omics Analysis Identifies PDK4 and ACOT1 as Metabolic Hub Genes Associated With Myocardial Fibrosis
Huan Liu1, Guanming Qi2, Shengrong Ouyang1
1Department of Biochemistry and Immunology, Capital Center for Children's Health, Capital Medical University, Capital Institute of Pediatrics, Beijing, China, shouer.com.cn.
Abstract:
Diabetic cardiomyopathy (DCM) is a critical pathological driver of heart failure in diabetic patients, primarily characterized by progressive myocardial fibrosis. Nevertheless, the core molecular network linking upstream metabolic dysregulation to the aberrant activation of downstream cardiac fibroblasts remains largely elusive. In this study, we combined in vivo and in vitro approaches with bioinformatics analysis. A high-fat diet-induced mouse model of diabetic myocardial fibrosis was established, and transcriptome sequencing was performed to screen for hub genes, which were subsequently validated in two independent DCM datasets. Single-cell RNA sequencing revealed that PDK4 and ACOT1 were upregulated in cardiac fibroblasts under pathological conditions. In vitro experiments confirmed that high glucose induced the expression of PDK4, ACOT1, and fibrotic markers in human primary cardiac fibroblasts. Molecular docking predicted a potential interaction between PDK4 and ACOT1. Collectively, our findings identify PDK4 and ACOT1 as evolutionarily conserved metabolic hub genes associated with myocardial fibrosis in DCM, suggesting a putative "metabolism-fibrosis axis" and providing potential therapeutic targets.
Insights
Diabetic cardiomyopathy involves heart fibrosis. Researchers identified PDK4 and ACOT1 as key metabolic genes driving this fibrosis, suggesting new therapeutic targets for diabetic heart conditions.
Area of Science:
- Biochemistry
- Cardiology
- Molecular Biology
Background:
- Diabetic cardiomyopathy (DCM) is a major cause of heart failure in diabetes.
- Myocardial fibrosis is a key characteristic of DCM, but the underlying molecular mechanisms are unclear.
- Understanding the link between metabolic issues and cardiac fibrosis is crucial for DCM treatment.
Purpose of the Study:
- To identify core molecular networks linking metabolic dysregulation to cardiac fibroblast activation in DCM.
- To investigate the roles of PDK4 and ACOT1 in diabetic myocardial fibrosis.
- To explore potential therapeutic targets for DCM.
Main Methods:
- Established a high-fat diet-induced mouse model of diabetic myocardial fibrosis.
- Utilized transcriptome sequencing and bioinformatics analysis to identify hub genes.
- Performed single-cell RNA sequencing and in vitro experiments on human cardiac fibroblasts.
- Conducted molecular docking to predict gene interactions.
Main Results:
- PDK4 and ACOT1 were identified as upregulated in cardiac fibroblasts in pathological conditions.
- High glucose conditions increased PDK4, ACOT1, and fibrotic marker expression in human cardiac fibroblasts.
- Molecular docking suggested a potential interaction between PDK4 and ACOT1.
- PDK4 and ACOT1 were validated as hub genes in independent DCM datasets.
Conclusions:
- PDK4 and ACOT1 are evolutionarily conserved metabolic hub genes linked to myocardial fibrosis in DCM.
- These findings suggest a novel "metabolism-fibrosis axis" in diabetic cardiomyopathy.
- PDK4 and ACOT1 represent potential therapeutic targets for managing DCM and its associated fibrosis.