The metabolism of [3-C-13]lactate in the rat brain is specific of a pyruvate carboxylase-deprived compartment

Lactate metabolism in the adult rat brain was investigated in relation with the concept of lactate trafficking between astrocytes and neurons. Wistar rats were infused intravenously with a solution containing either [3-C-13]l actate (534 mM) or both glucose (750 mM) and [3-C-13]lactate (534 mM). The time courses of both the concentration and C-13 enrichment of blood glucose and lactate were determined. The data indicated the occurrence of [3-C-13] actate recycling through liver gluconeogenesis. The yield of glucose labeli ng was, however, reduced when using the glucose-containing infusate. After a 20-min or 1-h infusion, perchloric acid extracts of the brain tissue were prepared and subsequently analyzed by C-13- and H-1-observed/C-13-edited N MR spectroscopy. The C-13 labeling of amino acids indicated that [3-C-13]la ctate was metabolized in the brain. Based on the alanine C3 enrichment, lac tate contribution to brain metabolism amounted to 35% under the most favora ble conditions used. By contrast with what happens with [1-C-13]glucose met abolism, no difference in glutamine C2 and C3 labeling was evidenced, indic ating that lactate was metabolized in a compartment deprived of pyruvate ca rboxylase activity. This result confirms, for the first time from an in viv o study, that lactate is more specifically a neuronal substrate.