Dietary Dityrosine Induces Mitochondrial Dysfunction by Diminished Thyroid Hormone Function in Mouse Myocardia

Area of Science:

• Biochemistry
• Cardiology
• Toxicology

Background:

• Oxidized tyrosine products (OTP) are found in high-protein foods.
• OTP intake is linked to oxidative stress and hypothalamic-pituitary-thyroid (HPT) axis disruption.

Purpose of the Study:

• To investigate the impact of OTP and dityrosine (Dityr) on mouse myocardial function and energy metabolism.
• To explore the molecular mechanisms underlying Dityr's effects on the myocardium.

Main Methods:

• Mice were administered tyrosine, Dityr, or OTP intragastrically for 35 days.
• H9c2 cardiac cells were incubated with Dityr.
• Assessed oxidative stress, myocardial injury, mitochondrial function, and energy metabolism.

Main Results:

• OTP and Dityr induced oxidative stress, redox imbalance, and myocardial injury in mice and H9c2 cells.
• Dityr impaired myocardial mitochondrial function and energy metabolism.
• Dityr interfered with T3 regulation via the PI3K/AKT/GSK3β pathway, causing cardiac damage.

Conclusions:

• Food-borne OTP, particularly Dityr, negatively impacts cardiac function.
• Dityr disrupts thyroid hormone signaling in the myocardium, leading to mitochondrial dysfunction and metabolic disorders.
• OTP exposure poses a risk to cardiovascular health through oxidative stress and hormonal disruption.