Hyperthyroidism evokes myocardial ceramide accumulation.

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Molecular Biology

Background:

• Thyroid hormones (THs) are crucial regulators of heart function.
• THs modulate cellular signaling pathways, including the sphingomyelin/ceramide pathway.
• The impact of hyperthyroidism on cardiac sphingolipid metabolism remains incompletely understood.

Purpose of the Study:

• To investigate the effects of experimentally induced hyperthyroidism on sphingolipid metabolism in rat cardiac muscle.
• To elucidate the specific changes in cardiac sphingolipid profiles under conditions of excess thyroid hormone.

Main Methods:

• Male Wistar rats were administered triiodothyronine (T3) for 10 days to induce hyperthyroidism.
• Cardiac left ventricle samples were collected from treated and control animals.
• Levels of various sphingolipids, enzyme activities, and key protein expressions were analyzed.

Main Results:

• Prolonged T3 treatment elevated cardiac sphinganine (SFA), sphingosine (SFO), ceramide (CER), and sphingomyelin (SM) levels.
• A significant decrease in cardiac sphingosine-1-phosphate (S1P) was observed.
• Hyperthyroidism activated AMP-activated protein kinase (AMPK) and increased mitochondrial protein expression (COX IV, β-HAD, CPT I, PGC1α).

Conclusions:

• Hyperthyroidism profoundly alters cardiac sphingolipid metabolism, increasing SFA and CER concentrations.
• Increased cardiac sphingomyelin (SM) may serve to maintain ceramide homeostasis, alongside reduced S1P levels.
• These metabolic shifts are associated with enhanced cardiac energy metabolism pathways.