Metabolism of Pyruvate and L-Lactate by Rat Adipose Tissue

Abstract

Abstract The metabolism of l-lactate and pyruvate, labeled uniformly with 14C, by epididymal fat pad tissue of fasted and fasted-refed rats was studied. In tissue of fasted-refed rats, pyruvate and l-lactate were utilized at equal rates. l-Lactate was nearly all converted into CO2 and fatty acids, and pyruvate into CO2, fatty acids, and l-lactate. The incorporation of 14C into glycerol was very low. l-Lactate was a better precursor of fatty acids than pyruvate. In tissue of fasted rats, pyruvate utilization was depressed, but still proceeded at an appreciable rate, and pyruvate carbon was incorporated into fatty acids and glycerol. The utilization of l-lactate by tissue of fasted rats was very low, and there was insignificant incorporation into lipids. Addition of unlabeled pyruvate or glucose to tissue of fasted rats metabolizing uniformly labeled l-lactate-14C increased 14C incorporation into CO2 and very markedly into lipid, but there was no net uptake of l-lactate. The 14C yields reflect exchange between labeled l-lactate and unlabeled pyruvate. Addition of malate, aspartate, α-ketoglutarate, and glutamate did not increase the utilization of uniformly labeled l-lactate-14C by tissue of fasted rats, but aspartate and α-ketoglutarate when added together stimulated l-lactate uptake, and incorporation of 14C into CO2 and lipids. Addition of oxalacetate and propionate increased to some extent 14C incorporation into CO2 and lipid, without appreciably stimulating l-lactate uptake. Addition of α-ketobutyrate or acetoacetate stimulated incorporation of l-lactate carbon into CO2 and lipids and net utilization of l-lactate by tissue of fasted rats. There was accumulation of α-hydroxybutyrate but not of β-hydroxybutyrate. Addition of acetate or β-hydroxybutyric acid was without effect. We conclude that in adipose tissue of rats there is no transfer of hydrogen equivalents from cytoplasm to mitochondria. When lipogenesis is pronounced, cytoplasmic hydrogen equivalents are all used in reductive biosynthesis; in the fasted state DPNH accumulates in the absence of lipogenesis, hydrogen equivalents from l-lactate oxidation cannot be utilized, and no l-lactate oxidation to pyruvate can occur.