Comparative analysis of metabolic and functional cardiac alterations in diet- and genetically induced mouse models of heart failure

ABSTRACT: This study aimed to elucidate the metabolic and functional alterations in heart failure in two mouse models with different heart failure phenotypes. C57BL/6J mice fed a high-fat diet (Black6 HF) and New Zealand Obese mice fed a standard diet (NZO SD) were analyzed compared to Black6 SD controls. Functional parameters of the heart were assessed through echocardiography. Additionally, plasma metabolites and tissue fibrosis were analyzed. Proteomics data from heart tissue were incorporated into a detailed kinetic model of central cardiac metabolism (CARDIOKIN1) to evaluate metabolic capacities. We demonstrate distinct structural and functional cardiac impairments, nutritional imbalances, and metabolic adaptations. Black6 HF mice exhibited cardiac dysfunction with normal ejection fraction, and decreased cardiac mass and inflammation, but without fibrosis while maintaining stable plasma nutrient composition. In contrast, NZO SD mice displayed heart failure with reduced ejection fraction, increased heart mass, significant derangement of circulating plasma nutrients, and mild fibrosis, but no inflammation. Proteomic analysis and kinetic modeling revealed that mitochondrial dysfunction and reduced ATP production capacity are key drivers of heart failure in Black6 HF mice, while NZO SD mice maintained ATP production capacity but showed significant alterations in substrate utilization capacities under variable energy demands. Our findings highlight the critical role of metabolic adaptation in heart failure emphasizing the importance of metabolic flexibility and efficiency. This study underscores the complex interplay between metabolic, structural, and functional changes in heart failure, providing valuable insights into and underpinning the different basis for treatment strategies for different forms of this syndrome.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Christoph Gille  

LAB HEAD: Nicolaus Berndt

PROVIDER: PXD057532 | Pride | 2026-04-27

REPOSITORIES: Pride