bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: March 19, 2025
The heart utilizes various nutrient sources for energy production, primarily favoring fatty acid oxidation. While ketones can be fuel substrates, ketolysis has been shown to dispensable development and function in mice. However, the long-term consequences of downregulation remain unknown. Here we demonstrate that ketone catabolism is essential preserving cardiac during aging. expression succinyl-CoA:3-ketoacid CoA transferase (SCOT), a rate-limiting enzyme ketolysis, decreases with aging female SCOT cardiomyocyte-specific knockout (cKO) mice exhibit normal at 10 weeks age but progressively develop dysfunction remodeling as they age, without overt hypertrophy both sexes. Notably, supplementation via ketogenic diet partially rescues contractile cKO mice, suggesting oxidation-independent mechanisms contribute cardiomyopathy caused by downregulation. These findings indicate crucial maintaining aging, confer cardioprotection independently
Language: Английский