Hepatic gluconeogenesis and Krebs cycle fluxes in a CCL4 model of acute liver failure

Rui A. Carvalho, John G. Jones, Chris McGuirk, A. Dean Sherry, Craig R. Malloy

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Acute liver failure was induced in rats by CCI4 administration and its effects on the hepatic Krebs cycle and gluconeogenic fluxes were evaluated in situ by 13C NMR isotopomer analysis of hepatic glucose following infusion of [U-13C]propionate. In fed animals, CCI4 injury caused a significant increase in relative gluconeogenic flux from 0.80 ± 0.10 to 1.34 ± 0.24 times the flux through citrate synthase (p < 0.01). In 24-h fasted animals, CCI4-injury also significantly increased relative gluconeogenic flux from 1.36 ± 0.16 to 1.80 ± 0.22 times the flux through citrate synthase (p < 0.01). Recycling of PEP via pyruvate and oxaloacetate was extensive under all conditions and was not significantly altered by CCI4 injury. CCI4 injury significantly reduced hepatic glucose output by 26% (42.8 ± 7.3 vs 58.1 ± 2.4 μmol/kg/min, p = 0.005), which was attributed to a 26% decrease in absolute gluconeogenic flux from PEP (85.6 ± 14.6 vs 116 ± 4.8 μmol/kg/min, p < 0.01). These changes were accompanied by a 47% reduction in absolute citrate synthase flux (90.6 ± 8.0 to 47.6 ± 8.0 μmol/kg/min, p < 0.005), indicating that oxidative Krebs cycle flux was more susceptible to CCI4 injury. The reduction in absolute fluxes indicate a significant loss of hepatic metabolic capacity, while the significant increases in relative gluconeogenic fluxes suggest a reorganization of metabolic activity towards preserving hepatic glucose output.

Original languageEnglish (US)
Pages (from-to)45-51
Number of pages7
JournalNMR in biomedicine
Volume15
Issue number1
DOIs
StatePublished - Mar 9 2002

Keywords

  • Glucose homeostasis
  • Hepatic glucose output
  • Intermediary metabolism
  • Krebs cycle flux

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy

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