Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion

Abstract

This study elucidates the role of metabolic remodeling in cardiac dysfunction induced by hyperthyroidism. Cardiac hypertrophy, structural remodeling, and expression of the genes associated with fatty acid metabolism were examined in rats treated with triiodothyronine (T 3 ) alone (8 mg/100 g body weight (BW), i.p.) for 15 days or along with a peroxisome proliferator-activated receptor alpha agonist bezafibrate (Bzf; 30 mg/100 g BW, oral) and were found to improve in the Bzf co-treated condition. Ultrastructure of mitochondria was damaged in T 3 -treated rat heart, which was prevented by Bzf co-administration. Hyperthyroidism-induced oxidative stress, reduction in cytochrome c oxidase activity, and myocardial ATP concentration were also significantly checked by Bzf. Heart function studied at different time points during the course of T 3 treatment shows an initial improvement and then a gradual but progressive decline with time, which is prevented by Bzf co-treatment. In summary, the results demonstrate that hyperthyroidism inflicts structural and functional damage to mitochondria, leading to energy depletion and cardiac dysfunction.

Hypothyroidism Is a Risk Factor for New-Onset Diabetes: A Cohort Study

“…Even low-normal free thyroxin levels in patients with euthyroidism have been associated with insulin resistance (22,23). Thyroid disease induces mitochondrial dysfunction (24)(25)(26)(27), and statins reduce levels of coenzyme Q10, a component of the electron transport chain involved in the process of ATP generation (28), also leading to mitochondrial dysfunction as well as causing reduced insulin release and pancreatic b-cell failure and contributing to the development of DM (29)(30)(31)(32). Downregulation of GLUT4 in adipocytes has also been shown to be a result of statin treatment, an effect that has been explained in terms of reduced isoprenoid biosynthesis (33).…”

Thyroid Hormones and the Heart; a Paradigm of Exquisite Fine Tuning, Combining Ancient Hellenic and Oriental Wisdom

“…However, Maity et al [12] have shown that after 5-8 days in the rat these begin to diminish. Heart failure in hyperthyroidism is well known, even without atrial fibrillation and disproportionate tachycardia.…”

“…Additionally, Maity et al [12] showed that ATP is increased very early (day 2) in the rat decreasing progressively from day 5 to 15. The rats received 8 μg/100 µg BW ip for 15 days.…”

“…Obviously it is a question of time and dosage. Maity et al [12] showed that T3 causes < more than 2 fold increase of lipid peroxidation. De Sibio et al [16] also found that in rats T3 at higher doses causes tissue oxidative stress and genotoxicity.…”

“…TH promote mitochondrial (MITO) genesis through a genomic action [13]. Cardiomyocytes have the highest volume of MITO (30%), of all cells according to Maity et al [12], who have shown that TH eventually diminish the mitochondrial membrane proteins prohibitin and VDAC, suggesting a noxious action on the mitochondria. Also, it is well known that TH can increase angiogenesis [14].…”