Glucose and insulin-induced inhibition of fatty acid oxidation: The glucose-fatty acid cycle reversed

Labros S. Sidossis, Robert R. Wolfe

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

In this study we have investigated a hypothesis that proposes the reverse of the so-called 'glucose-fatty acid cycle,' i.e., that accelerated carbohydrate metabolism directly inhibits fatty acid oxidation. We studied normal volunteers in the basal state and during a hyperinsulinemic, hyperglycemic clamp (plasma insulin = 1,789 ± 119 pmol/l, plasma glucose = 7.7 ± 0.2 mmol/l). We quantified fat oxidation using indirect calorimetry and stable isotopes ([1- 13C]oleate). Plasma oleate enrichment and free fatty acid (FFA) concentration were kept constant by means of infusion of lipids and heparin. Glucose oxidation increased from basal 6.2 ± 0.8 to 22.3 ± 1.4 μmol · kg -1 · min -1 during the clamp (P < 0.01). Total (indirect calorimetry) and plasma fatty acid oxidation (isotopic determination) decreased from 2.6 ± 0.2 to 0.4 ± 0.3 (P < 0.01) and 2.2 ± 0.2 to 1.4 ± 0.1 μmol · kg -1 · min -1 (P < 0.05), respectively. We conclude that under the conditions of the present experiment, glucose and/or insulin directly inhibits fatty acid oxidation. Our findings suggest that, contrary to the prediction of the glucose-fatty acid cycle, the intracellular availability of glucose (rather than FFA) determines the nature of substrate oxidation in human subjects.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume270
Issue number4 33-4
StatePublished - 1996

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Fatty Acids
Insulin
Glucose
Oxidation
Plasmas
Indirect Calorimetry
Clamping devices
Calorimetry
Oleic Acid
Nonesterified Fatty Acids
Carbohydrate Metabolism
Isotopes
Heparin
Healthy Volunteers
Fats
Availability
Lipids
Substrates
Experiments

Keywords

  • carnitine acetyltransferase
  • diabetes
  • malonyl-coenzyme A
  • mitochondria
  • obesity

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry
  • Physiology (medical)

Cite this

Glucose and insulin-induced inhibition of fatty acid oxidation : The glucose-fatty acid cycle reversed. / Sidossis, Labros S.; Wolfe, Robert R.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 270, No. 4 33-4, 1996.

Research output: Contribution to journalArticle

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