title: Regulation of intermediary metabolism in rat cardiac myocyte by extracellular glycerol.
abstract: 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.
authors.affiliation: UMR 1154 INRA-UPS, Faculty of Pharmacy, 5 rue Jean-Baptiste Clément, 92290 Chatenay-Malabry, France.
authors.forename: Ségolène
authors.initials: S
authors.lastname: Gambert
authors.forename: Cécile
authors.initials: C
authors.lastname: Héliès-Toussaint
authors.forename: Alain
authors.initials: A
authors.lastname: Grynberg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002210:Caprylates / Q000378:metabolism; D002478:Cells, Cultured; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D008316:Malonyl Coenzyme A / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002210:Caprylates; D005227:Fatty Acids; D010743:Phospholipids; D019308:Palmitic Acid; D008316:Malonyl Coenzyme A; D006003:Glycogen; D005947:Glucose; C031492:octanoic acid; D005990:Glycerol; D010100:Oxygen