Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy

Area of Science:

• Cardiology
• Metabolic Diseases
• Molecular Biology

Background:

• Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes mellitus (DM).
• The mechanisms underlying DCM, particularly concerning myocardial calcium (Ca²⁺) homeostasis, are not fully understood.
• Ketogenic diet (KD) is being explored for potential therapeutic benefits in various conditions, including cardiovascular diseases.

Purpose of the Study:

• To investigate the effects of a ketogenic diet (KD) on Ca²⁺ homeostasis and cardiac electrophysiology in a rat model of diabetic cardiomyopathy (DCM).
• To elucidate the molecular mechanisms by which KD may offer cardioprotection in the context of diabetes.

Main Methods:

• Induction of diabetes mellitus (DM) in male Wistar rats using streptozotocin.
• Treatment of DM rats with either a normal diet (ND) or a ketogenic diet (KD) for 6 weeks.
• Assessment of myocardial function, electrophysiology (QTc interval, action potential duration), Ca²⁺ handling proteins (Western blot), and ion channel activity (in vivo ventricular preparations).

Main Results:

• DM rats on ND showed prolonged QTc interval and action potential duration compared to KD-treated rats.
• DM rats on ND exhibited impaired Ca²⁺ homeostasis, including reduced intracellular Ca²⁺ transients and sarcoplasmic reticular Ca²⁺ content.
• KD treatment normalized Ca²⁺ handling proteins, reduced Ca²⁺ leak, and decreased reactive oxygen species, Na⁺/H⁺ exchanger currents, and late Na⁺ currents in DM rats.

Conclusions:

• Ketogenic diet (KD) attenuates the detrimental effects of diabetes mellitus (DM) on myocardial Ca²⁺ homeostasis and electrophysiology.
• KD may protect against diabetic cardiomyopathy by restoring normal Na⁺ and Ca²⁺ handling in the heart.
• These findings suggest KD as a potential therapeutic strategy for managing diabetic cardiomyopathy.