Tetramethylpyrazine (TMP) switches energy signalling from the PKCζ-GLUT4-glucose pathway back to the SIRT1-CD36-fatty acid pathway similar to resveratrol to ameliorate cardiac myocyte lipotoxicity

• Energy metabolism.
• Cardiomyoblast lipotoxicity.
• Switches energy signalling from the PKCζ–GLUT4–glucose pathway back to the SIRT1–CD36–fatty acid pathway.

Fatty acids and glucose are the main energy sources for the heart. Energy metabolic imbalance can cause many heart dysfunctions. Cardiomyocytes can switch to using fatty acids or glucose as an energy source. Palmitic acid (PA) treatment induces lipoptoxity and loss of mitochondrial function. We utilised PA treatment to simulate hyperlipidaemia and subsequently investigated the protective effects of tetramethylpyrazine (TMP) on the PAinduced cluster of differentiation 36 (CD36) and glucose transporter type 4 (GLUT4) signalling switch. The results showed that TMP can protect H9c2 cells and neonatal rat cardiomyocytes from PA-induced lipotoxicity similar to resveratrol significantly activated sirtuin1 to increase CD36 and decrease GLUT4 pathway proteins following treatment with PA, and switch the energy signalling GLUT4 pathway back to the CD36 pathway to ameliorate cardiac myocyte lipotoxicity and rescue the impaired energy metabolism. Therefore, we recommend TMP as a more efficient herbal component for maintaining the energy metabolism of the heart.