Western diet triggers cardiac dysfunction in heterozygous Mybpc3-targeted knock-in mice: A two-hit model of hypertrophic cardiomyopathy.

ABSTRACT:

Background and aim

Phenotypic expression of hypertrophic cardiomyopathy (HCM) and disease course are associated with unfavorable metabolic health. We investigated if Western diet (WD) feeding is sufficient to trigger cardiac hypertrophy and dysfunction in heterozygous (HET) Mybpc3 _c.772G>A knock-in mice.

Methods and results

Wild-type (WT) and HET mice (3-months-old) were fed a WD or normal chow (NC) for 8 weeks. Metabolomic analyses on serum revealed systemic metabolic derailment in WD-fed WT and HET mice. Strikingly, only WD-fed HET mice developed cardiac hypertrophy and dysfunction, which was not driven by aggravated cardiac myosin binding protein-C haploinsufficiency. WD reduced oxidative phosphorylation and increased toxic lipids in the heart irrespecti

SUBMITTER: Nollet EE 

PROVIDER: S-EPMC11708371 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature