Effect of dichloroacetate on carbohydrate and lipid metabolism of isolated hepatocytes

David W. Crabb, James P. Mapes, Richard W. Boersma, Robert A. Harris

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Dichloroacetate has effects upon hepatic metabolism which are profoundly different from its effects on heart, skeletal muscle, and adipose tissue metabolism. With hepatocytes prepared from meal-fed rats, dichloroacetate was found to activate pyruvate dehydrogenase, to increase the utilization of lactate and pyruvate without effecting an increase in the net utilization of glucose, to increase the rate of fatty acid synthesis, and to decrease slightly [1-14C]oleate oxidation to 14CO2 without decreasing ketone body formation. With hepatocytes isolated from 48-h-starved rats, dichloroacetate was found to activate pyruvate dehydrogenase, to have no influence on net glucose utilization, to inhibit gluconeogenesis slightly with lactate as substrate, and to stimulate gluconeogenesis significantly with alanine as substrate. The stimulation of fatty acid synthesis by dichloroacetate suggests that the activity of pyruvate dehydrogenase can be rate determining for fatty acid synthesis in isolated liver cells. The minor effects of dichloroacetate on gluconeogenesis suggest that the regulation of pyruvate dehydrogenase is only of marginal importance in the control of gluconeogenesis.

Original languageEnglish (US)
Pages (from-to)658-665
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume173
Issue number2
DOIs
StatePublished - Apr 1976

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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