Metabolic regulation is inextricably linked with cardiac function.
Fatty acid metabolism is a significant mechanism for creating energy for the heart. However, cardiomyocytes are able to switch the
fatty acids or
glucose, depending on different situations, such as
ischemia or
anoxia. Lipotoxicity in
obesity causes impairments in energy metabolism and apoptosis in cardiomyocytes. We utilized the treatment of H9c2 cardiomyoblast cells
palmitic acid (PA) as a model for
hyperlipidemia to investigate the signaling mechanisms involved in these processes. Our results show PA induces time- and dose-dependent lipotoxicity in H9c2 cells. Moreover, PA enhances cluster of differentiation 36 (CD36) and reduces
glucose transporter type 4 (GLUT4) pathway
protein levels following a short period of treatment, but cells switch from CD36 back to the GLUT4 pathway after during long-term exposure to PA. As
sirtuin 1 (
SIRT1) and
protein kinase Cζ (PKCζ) play important roles in CD36 and GLUT4 translocation, we used the
SIRT1 activator
resveratrol and si-PKCζ to identify the switches in metabolism. Although PA reduced CD36 and increased GLUT4 metabolic pathway
proteins, when we pretreated cells with
resveratrol to activate
SIRT1 or transfected si-PKCζ, both were able to significantly increase CD36 metabolic pathway
proteins and reduce GLUT4 pathway
proteins. High-fat diets affect energy metabolism pathways in both normal and aging rats and involve switching the energy source from the CD36 pathway to GLUT4. In conclusion, PA and high-fat diets cause lipotoxicity in vivo and in vitro and adversely switch the energy source from the CD36 pathway to the GLUT4 pathway.