The Metabolism of [3‐13C]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 [3‐13C]lactate (534 mM) or both glucose (750 mM) and [3‐13C]lactate (534 mM). The time courses of both the concentration and 13C enrichment of blood glucose and lactate were determined. The data indicated the occurrence of [3‐13C]lactate recycling through liver gluconeogenesis. The yield of glucose labeling 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 13C‐ and 1H‐observed/13C‐edited NMR spectroscopy. The 13C labeling of amino acids indicated that [3‐13C]lactate was metabolized in the brain. Based on the alanine C3 enrichment, lactate contribution to brain metabolism amounted to 35% under the most favorable conditions used. By contrast with what happens with [1‐13C]glucose metabolism, no difference in glutamine C2 and C3 labeling was evidenced, indicating that lactate was metabolized in a compartment deprived of pyruvate carboxylase activity. This result confirms, for the first time from an in vivo study, that lactate is more specifically a neuronal substrate.