Objectives:
Overfeeding with a high carbohydrate and/or high-fat diet induces metabolic syndrome (MetS) in humans, which is characterized by insulin-resistance. Long life span leads to increases in the ratio of aged humans in populations and an important percentage of the aged humans has insulin-resistance. There is a close relationship between insulin resistance and cardiac dysfunction, at least, via uncontrolled production of reactive oxygen species, while mitochondrial dysfunction plays an important role in that relation. To explore that relation, we aimed to examine the possible cardioprotective effect of a mitochondria-targeting antioxidant by using electrophysiological and histological examinations.
Materials and Methods:
We used Wistar male rats in three groups as; those that were 24-month-old (elderly group; n=7), adults fed with 32% sucrose diet (MetS-group; 6-month-old; n=7), and adults fed with standard food (Control group; 6-month-old, n=7). MetS was confirmed with high blood glucose, oral glucose tolerance test, and serum insulin levels. Cardiomyocytes either treated with an antioxidant MitoTEMPO were isolated from the left ventricle by enzymatic method, and the ultrastructure and function of mitochondria as well as adenosine triphosphate (ATP)- dependent K+-channel currents (IKATP; patch-clamp technique) were evaluated.
Results:
There were marked increases in the fragmentation of mitochondria, depolarization in the membrane potential, and the production of ROS in insulin-resistant cardiomyocytes. There were significant decreases in IKATP and ATP level (p<0.05) in the aged-cardiomyocytes. Incubation of those insulin-resistant or aged-cardiomyocytes with a mitochondria-targeting antioxidant MitoTEMPO (0.1 μM, 4-5 h at 37°C) provided marked reverses in those parameters.
Conclusion:
Overall, the present data strongly indicate that mitochondria-targeting antioxidant application can exert cardioprotective effects in either insulin-resistant MetS or aged mammalians, providing strong implications on mitochondria as a novel strategy for prevention/treatment of cardiovascular diseases.
Keywords: Ageing, Metabolic Syndrome, Insulin Resistance, Cardiac Function, Mitochondria, Antioxidants
