Lycopene Regulates Dietary Dityrosine-Induced Mitochondrial-Lipid Homeostasis by Increasing Mitochondrial Complex Activity.

Abstract

Dityrosine (DT), a marker of protein oxidation, is widely found in many high-protein foods. Dietary intake of DT induces myocardial oxidative stress injury and impairs energy metabolism. Lycopene is a common dietary supplement with antioxidant and mitochondrial-lipid homeostasis modulating abilities. This study aimed to examine the effects of lycopene on DT-induced disturbances in myocardial function and energy metabolism. Four-week-old C57BL/6J mice received intragastric administration of either tyrosine (420µg kg-1 BW), DT (420µg kg-1 BW), or lycopene at high (10mg kg-1 BW) and low (5mg kg-1 BW) doses for 35 days. Lycopene administration effectively reduced oxidative stress, cardiac fatty acid accumulation, and cardiac hypertrophy and improved mitochondrial performance in DT-induced mice. In vitro experiments in H9c2 cells showed that DT directly inhibited the activity of the respiratory chain complex, whereas oxidative phosphorylation and β-oxidation gene expression is upregulated. Lycopene enhanced the activity of the complexes and inhibited ROS production caused by compensatory regulation. Lycopene improves DT-mediated myocardial energy homeostasis disorder by promoting the activity of respiratory chain complexes I and IV and alleviates the accumulation of cardiac fatty acids and myocardial hypertrophy.