Structural and functional changes in heart mitochondria from sucrose-fed hypertriglyceridemic rats

Area of Science:

• Biochemistry
• Cardiology
• Metabolic Disorders

Background:

• Sugar-induced hypertriglyceridemia (HTG) impairs cardiac performance in rats, particularly when using glucose as fuel.
• Energy transfer and glycolytic flux are diminished in the HTG heart compared to controls.

Purpose of the Study:

• To investigate the biochemical alterations in non-glycolytic energy systems within the HTG heart.
• To elucidate the mechanisms behind impaired cardiac energy metabolism in sugar-induced hypertriglyceridemia.

Main Methods:

• Assessed total and mitochondrial creatine kinase (CK) and adenylate kinase (AK) activities in myocardial tissue and isolated mitochondria.
• Measured respiratory rates, 2-oxoglutarate dehydrogenase activity, and cytochrome content in HTG and control heart mitochondria.
• Analyzed fatty acid and phospholipid composition, cholesterol content, and membrane rigidity of mitochondrial membranes.

Main Results:

• Total CK activity decreased by 30% and mitochondrial CK (mitCK) by 45% in HTG hearts.
• Adenylate kinase (AK) activity was 20% lower in HTG hearts.
• Mitochondrial oxidative capacity (respiratory rates with 2-OG and pyruvate/malate) and 2-OG dehydrogenase activity were higher in HTG mitochondria, with increased membrane rigidity and potential, despite similar cytochrome content.

Conclusions:

• Energy transfer deficiency in HTG hearts is linked to impaired mitCK and AK function.
• This impairment leads to uncoupling between ATP production and consumption sites, despite preserved or enhanced mitochondrial oxidative capacity.
• Altered mitochondrial membrane fatty acid composition contributes to increased rigidity and membrane potential in HTG hearts.