Metabolic changes in the myocardium of hamsters with hereditary muscular dystrophy

Area of Science:

• Biochemistry
• Cardiology
• Metabolic Research

Background:

• Carnitine deficiency is a known cause of reduced fatty acid oxidation in cardiomyopathies.
• However, this mechanism does not explain the depressed fatty acid oxidation observed in BIO 14.6 strain hamsters.

Purpose of the Study:

• To investigate the cause of depressed fatty acid oxidation in the cardiac lesion of BIO 14.6 hamsters.
• To determine if carnitine levels are a factor in this specific cardiomyopathy.

Main Methods:

• Assessed CO2 production from labeled fatty acids (acetate, butyrate, octanoate, palmitate) in heart homogenates with and without carnitine.
• Measured the activity of carnitine palmitoyltransferase and fatty acid activating enzymes.
• Examined the oxidation of succinate, acetyl CoA, pyruvate, and oxoglutarate.
• Analyzed myocardial triglyceride content and palmitate esterification.

Main Results:

• Despite normal carnitine levels, fatty acid oxidation was depressed in diseased hamsters.
• Oxidation of succinate and acetyl CoA was reduced by approximately 40%.
• Pyruvate and oxoglutarate oxidation was reduced by 60-70%, with no reduction in CO2 production from specific pyruvate and oxoglutarate isotopes.

Conclusions:

• The depressed fatty acid oxidation in this hamster cardiomyopathy is not due to carnitine deficiency.
• The varying degrees of substrate oxidation suggest complex alterations in the tricarboxylic acid cycle metabolism or substrate utilization pathways.