Effect of dichloroacetate on carbohydrate and lipid metabolism of isolated hepatocytes

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

Research output: Contribution to journalArticle

29 Citations (Scopus)

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

Fingerprint

Carbohydrate Metabolism
Pyruvic Acid
Lipid Metabolism
Gluconeogenesis
Hepatocytes
Oxidoreductases
Fatty Acids
Metabolism
Rats
Lactic Acid
Glucose
Ketone Bodies
Liver
Substrates
Oleic Acid
Alanine
Meals
Muscle
Adipose Tissue
Myocardium

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Effect of dichloroacetate on carbohydrate and lipid metabolism of isolated hepatocytes. / Crabb, David; Mapes, James P.; Boersma, Richard W.; Harris, Robert.

In: Archives of Biochemistry and Biophysics, Vol. 173, No. 2, 1976, p. 658-665.

Research output: Contribution to journalArticle

@article{4c0f370b4ce445f58c3bd10f6955b0d7,
title = "Effect of dichloroacetate on carbohydrate and lipid metabolism of isolated hepatocytes",
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.",
author = "David Crabb and Mapes, {James P.} and Boersma, {Richard W.} and Robert Harris",
year = "1976",
doi = "10.1016/0003-9861(76)90303-9",
language = "English",
volume = "173",
pages = "658--665",
journal = "Archives of Biochemistry and Biophysics",
issn = "0003-9861",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Effect of dichloroacetate on carbohydrate and lipid metabolism of isolated hepatocytes

AU - Crabb, David

AU - Mapes, James P.

AU - Boersma, Richard W.

AU - Harris, Robert

PY - 1976

Y1 - 1976

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0017153013&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0017153013&partnerID=8YFLogxK

U2 - 10.1016/0003-9861(76)90303-9

DO - 10.1016/0003-9861(76)90303-9

M3 - Article

C2 - 1275512

AN - SCOPUS:0017153013

VL - 173

SP - 658

EP - 665

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

IS - 2

ER -