Glucose plus insulin regulate fat oxidation by controlling the rate of fatty acid entry into the mitochondria

Labros S. Sidossis, Charles A. Stuart, Gerald I. Shulman, Gary D. Lopaschuk, Robert R. Wolfe

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

We tested the hypothesis that glucose plus insulin determine the rate of fat oxidation in humans by controlling the rate of fatty acid entrance into the mitochondria. We gave constant infusions of [1-13C]oleate, a long- chain fatty acid, and [1-14C]octanoate, a medium-chain fatty acid, for 3 h in seven volunteers (basal). Immediately after the basal period, a hyperinsulinemic (insulin infusion = 120 mU · m-2 · min-1), hyperglycemic (plasma glucose = 140 mg/dl) clamp was started and continued for 5 h. During the last 3 h of the clamp, the infusions of [1-13C]oleate and [1-14C]octanoate were repeated. Intracellular acylcarnitine concentrations were measured in muscle biopsies obtained before and after the clamp. Plasma oleate enrichment and FFA concentration were kept constant by means of variable infusions of lipids and heparin. Oleate, but not octanoate, requires carnitine binding to gain access to the mitochondrial matrix; hence, if glucose and/or insulin limit long-chain fatty acid entrance into the mitochondria, then, during the clamp, long-chain acylcarnitine formation should be decreased, causing a decrease in oleate, but not octanoate, oxidation. Oleate oxidation decreased from the basal value of 0.7 ± 0.1 to 0.4 ± 0.1 μmol · kg-1 · min-1 (P < 0.05). In contrast, octanoate oxidation remained unchanged. Long-chain acyl-carnitine concentration decreased from 855 ± 271 in the basal state to 376 ± 83 nmol/gram dry weight during the clamp (P < 0.05). We conclude that glucose and/or insulin determine fatty acid oxidation by controlling the rate of long-chain fatty acid entrance into the mitochondria.

Original languageEnglish (US)
Pages (from-to)2244-2250
Number of pages7
JournalJournal of Clinical Investigation
Volume98
Issue number10
StatePublished - Nov 15 1996

Fingerprint

Oleic Acid
Mitochondria
Fatty Acids
Fats
Insulin
Glucose
Carnitine
Heparin
Volunteers
octanoic acid
Lipids
Biopsy
Weights and Measures
Muscles

Keywords

  • carnitine palmitoyltransferase
  • diabetes
  • malonyl-coenzyme A
  • medium chain fatty acids
  • obesity

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sidossis, L. S., Stuart, C. A., Shulman, G. I., Lopaschuk, G. D., & Wolfe, R. R. (1996). Glucose plus insulin regulate fat oxidation by controlling the rate of fatty acid entry into the mitochondria. Journal of Clinical Investigation, 98(10), 2244-2250.

Glucose plus insulin regulate fat oxidation by controlling the rate of fatty acid entry into the mitochondria. / Sidossis, Labros S.; Stuart, Charles A.; Shulman, Gerald I.; Lopaschuk, Gary D.; Wolfe, Robert R.

In: Journal of Clinical Investigation, Vol. 98, No. 10, 15.11.1996, p. 2244-2250.

Research output: Contribution to journalArticle

Sidossis, LS, Stuart, CA, Shulman, GI, Lopaschuk, GD & Wolfe, RR 1996, 'Glucose plus insulin regulate fat oxidation by controlling the rate of fatty acid entry into the mitochondria', Journal of Clinical Investigation, vol. 98, no. 10, pp. 2244-2250.
Sidossis, Labros S. ; Stuart, Charles A. ; Shulman, Gerald I. ; Lopaschuk, Gary D. ; Wolfe, Robert R. / Glucose plus insulin regulate fat oxidation by controlling the rate of fatty acid entry into the mitochondria. In: Journal of Clinical Investigation. 1996 ; Vol. 98, No. 10. pp. 2244-2250.
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