Direct Regulation of Myocardial Triglyceride Metabolism by the Cardiomyocyte Circadian Clock

CCM mice exhibited altered myocardial response to chronic high fat feeding, indicating that the cardiomyocyte clock may regulate myocardial triglyceride metabolism.

• A genetic model of disrupted clock function in cardiomyocytes showed significant changes in the transcriptome and lipidome.
• Myocardial triglyceride levels, net triglyceride synthesis, and lipolysis demonstrated time-of-day-dependent oscillations that were reduced in CCM hearts.
• The cardiomyocyte clock may influence triglyceride turnover by inactivating hormone-sensitive lipase during the active/awake phase.
• High fat feeding at the end of the active/awake phase led to increased net triglyceride synthesis and cardiac steatosis.
• These findings suggest a connection between circadian misalignment and accelerated metabolic pathologies.

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