In support of the roles of malonyl-CoA and carnitine acyltransferase I in the regulation of hepatic fatty acid oxidation andketogenesis

J. D. McGarry, D. W. Foster

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

The rate of fatty acid synthesis in hepatocytes from meal-fed rats was manipulated over a wide range using glucose, lactate, and pyruvate to drive the system maximally, and glucagon, 5-(tetradecyloxy)-2-furoic acid (RMI 14,514), or a combination of both agents to inhibit lipogenesis. Measurements were made of cellular malonyl-CoA levels, long chain acylcarnitine concentration, and [1-14C]oleate oxidation to total acid-soluble products, ketone bodies, and CO2. Regardless of the intervention employed, the rate of fatty acid synthesis correlated positively with the tissue malonyl-CoA concentration; both of these parameters were inversely related to the concentration of long chain acylcarnitine which, in turn, was directly proportional to the rate of fatty acid oxidation. Addition of glucagon, RMI 14,514, and carnitine to hepatocytes from meal-fed rats abolished the synthesis of malonyl-CoA, stopped lipogenesis, and stimulated fatty acid oxidation and ketogenesis to rates equivalent to those seen in hepatocytes from fasted animals. The data provide further support for the central roles of malonyl-CoA and carnitine acyl-transferase I in the coordination of hepatic fatty acid synthesis and oxidation. They also establish that the changes in fatty acid oxidation and ketogenesis produced by fasting can be entirely accounted for by removal of the malonyl-CoA-mediated inhibition of carnitine acyltransferase I activity, coupled with a rise in hepatic carnitine content.

Original languageEnglish (US)
Pages (from-to)8163-8168
Number of pages6
JournalJournal of Biological Chemistry
Volume254
Issue number17
StatePublished - Dec 1 1979

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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