2025/04/09 by Mariapia Chindamo, Hassib Chehade, Anthony Sordet +8
Biochemistry, Genetics and Molecular Biology · Medicine · #Birth, Development, and Health #Cardiovascular Function and Risk Factors #Mitochondrial Function and Pathology
paper · doi:10.1016/j.nut.2025.112796
openalex publication_date 2025/04/09 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
Heart disease is a leading cause of death worldwide, with its prevalence exacerbated by inadequate nutritional intake. Particularly concerning is the elevated risk induced by imbalanced nutrition during development, which can impact lifelong heart health. Recent research has underscored mitochondrial dysregulation as a pivotal mechanism driving the enduring consequences of nutritional excess. Building upon previous findings wherein a maternal high-fat diet (HFD) led to cardiac hypertrophy and fibrosis, our current study aimed to evaluate the impact of such a challenge on myocardial mitochondrial function. Female rats were fed a chow diet or HFD during gestation and lactation. The hearts of male offspring were analyzed at adulthood. Mitochondrial DNA abundance was evaluated by quantitative polymerase chain reaction. Proteins involved in mitochondrial biogenesis, fusion, fission, damage to the electron transport chain, metabolism, cell death, proliferation, and inflammation were measured by western blot. Mitochondrial clearance was evaluated by the measurement of mitophagy markers on isolated mitochondria. Lipids were visualized by histologic approaches. We detected decreased cardiac mitochondrial fission factor and mitochondrial adenosine triphosphate synthase beta subunit and increased Parkin, pro-tumor necrosis factor alpha, and pro-interleukin 1 beta protein levels associated with decreased microtubule-associated protein 1A/1B light chain 3B levels in cardiac mitochondrial fraction, with a tendency for increased Oil Red O staining in the adult hearts of male offspring exposed to HFD. Maternal exposure to HFD enhanced mitochondrial damage and impaired fission and clearance in offspring hearts at adulthood. These alterations were associated with altered expression of proteins involved in the mitochondrial electron transport chain coupled with a propensity for increased fatty acid accumulation and elevated proinflammatory markers. • Maternal exposure to a high-fat diet altered mitochondrial dynamics in the hearts of male offspring at adulthood by enhancing mitochondrial damage and impairing fission and clearance. • Maternal exposure to a high-fat diet decreased the expression of mitochondrial adenosine triphosphate synthase beta subunit, involved in complex V of the mitochondrial electron transport chain. • Maternal exposure to a high-fat diet tended to increase fatty acid storage and elevated proinflammatory markers in the hearts of male offspring at adulthood.