Regulation of intermediary metabolism in rat cardiac myocyte by extracellular glycerol

In the human heart, although all substrates compete for energy production, fatty acids (FA) represent the main substrate for ATP production. In the healthy heart, a balance between FA and carbohydrate utilization ensures that energy supply matches demand. This study was carried out to evaluate, in a model of spontaneously beating neonatal rat cardiomyocytes in culture, the hypothesis that glycerol could play a central role in the metabolic control of the routes involving long chain FAs and may then affect the balance between beta-oxidation and glucose oxidation. The intracellular-free glycerol significantly increased with extracellular glycerol concentration (0 to 660 microM). The synthesis of phospholipids was significantly increased in parallel with both extracellular glycerol (1.5 and 14.8 nmol glycerol/mg protein, at 82 and 660 microM of extracellular glycerol, respectively). The oxidation of glycerol increased proportionally to extracellular glycerol concentration (from 1 to 3 nmol glycerol/mg protein, at 82 microM and 660 microM extracellular glycerol, respectively, P<0.001). At its maximum, this oxidation represented 15% of the glucose oxidation, which was not affected by glycerol extracellular supply or intracellular availability. Conversely, extracellular glycerol significantly reduced the palmitate oxidation above (-47% at 660 microM glycerol), but not octanoate oxidation. Investigations on the mechanism of the decreased palmitate oxidation reveals a glycerol-dependent increase in malonyl-CoA associated with a significant decrease in CPT-1 activity which accounts for the difference between palmitate and octanoate. These results clearly demonstrate the importance of glycerol in regulating the cardiac metabolic pathways and energy balance.