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Updated: Jan 13, 2026

Methods for the Determination of Rates of Glucose and Fatty Acid Oxidation in the Isolated Working Rat Heart
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Ketone Catabolism Is Essential for Maintaining Normal Heart Function During Aging.

Mariko Aoyagi Keller1, Michinari Nakamura1

  • 1Department of Cell Biology and Molecular Medicine Rutgers New Jersey Medical School Newark NJ USA.

Journal of the American Heart Association
|October 28, 2025
PubMed
Summary

Ketone catabolism is vital for maintaining heart function as mice age. Impaired ketolysis leads to cardiac dysfunction, but ketogenic diets offer partial protection, suggesting ketone oxidation-independent benefits.

Keywords:
cardiac remodelingheart failurehypertrophyketogenic dietketolysisketoneketone oxidation

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Area of Science:

  • Cardiovascular Research
  • Metabolic Science
  • Aging Biology

Background:

  • The heart primarily utilizes fatty acids for energy but can use ketones.
  • Ketolysis is not essential for heart development but its long-term effects are unknown.
  • Cardiac ketone metabolism's role in aging remains unexplored.

Purpose of the Study:

  • To investigate the functional significance of cardiac ketolysis during aging.
  • To determine the impact of impaired ketolysis on heart function over time.
  • To assess the effects of ketogenic diets on cardiac function in a model of impaired ketolysis.

Main Methods:

  • Utilized a mouse model with cardiomyocyte-specific knockout of SCOT (succinyl-CoA:3-ketoacid CoA transferase), a key ketolysis enzyme.
  • Administered a ketogenic diet to evaluate exogenous ketone supplementation.
  • Assessed cardiac function and remodeling in aging mice with impaired ketolysis.

Main Results:

  • Cardiac SCOT expression declines with age in mice.
  • SCOT knockout mice develop age-dependent cardiac dysfunction and remodeling.
  • Ketogenic diet partially rescues cardiac contractile dysfunction, indicating oxidation-independent mechanisms.

Conclusions:

  • Ketone catabolism is essential for preserving cardiac function during aging.
  • Ketones provide cardioprotection through mechanisms beyond simple oxidation.
  • Downregulation of ketolysis contributes to age-related cardiac dysfunction.