title: Inhibitory effect of tumor necrosis factor α on gluconeogenesis in perfused rat liver.
abstract: Tumor necrosis factor α (TNFα) is a cytokine involved in many metabolic responses in both normal and pathological states. Considering that the effects of TNFα on hepatic gluconeogenesis are inconclusive, we investigated the influence of this cytokine in gluconeogenesis from various glucose precursors. TNFα (10 μg/kg) was intravenously injected in rats; 6 h later, gluconeogenesis from alanine, lactate, glutamine, glycerol, and several related metabolic parameters were evaluated in situ perfused liver. TNFα reduced the hepatic glucose production (p < 0.001), increased the pyruvate production (p < 0.01), and had no effect on the lactate and urea production from alanine. TNFα also reduced the glucose production (p < 0.01), but had no effect on the pyruvate production from lactate. In addition, TNFα did not alter the hepatic glucose production from glutamine nor from glycerol. It can be concluded that the TNFα inhibited hepatic gluconeogenesis from alanine and lactate, which enter in gluconeogenic pathway before the pyruvate carboxylase step, but not from glutamine and glycerol, which enter in this pathway after the pyruvate carboxylase step, suggesting an important role of this metabolic step in the changes mediated by TNFα.
authors.affiliation: Department of Physiological Sciences, State University of Londrina, Londrina, PR 86051-990, Brazil.
authors.forename: Aline Franco
authors.initials: AF
authors.lastname: da Rocha
authors.forename: Thaís Fernanda
authors.initials: TF
authors.lastname: Liboni
authors.forename: Carolina Campos Lima
authors.initials: CC
authors.lastname: Moreira
authors.forename: Daniele Romani
authors.initials: DR
authors.lastname: Miksza
authors.forename: Camila Oliveira
authors.initials: CO
authors.lastname: de Souza
authors.forename: Flaviane
authors.initials: F
authors.lastname: de Fatima Silva
authors.forename: Glaucia Regina
authors.initials: GR
authors.lastname: Borba-Murad
authors.forename: Roberto Barbosa
authors.initials: RB
authors.lastname: Bazotte
authors.forename: Helenir Medri
authors.initials: HM
authors.lastname: de Souza
mesh_terms: D000409:Alanine / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D005943:Gluconeogenesis; D005947:Glucose / Q000096:biosynthesis; D005973:Glutamine / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014508:Urea / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; D019344:Lactic Acid; D019289:Pyruvic Acid; D014508:Urea; D005947:Glucose; D000409:Alanine; D005990:Glycerol