Effect of insulin on oxidative and nonoxidative pathways of free fatty acid metabolism in human obesity

L. C. Groop, R. C. Bonadonna, D. C. Simonson, A. S. Petrides, M. Shank, R. A. DeFronzo

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

The dose-response relationship between the plasma insulin concentration and oxidative and nonoxidative pathways of free fatty acid (FFA) metabolism was examined in 11 obese and 7 lean subjects using a stepwise insulin clamp technique in combination with indirect calorimetry and infusion of [1- 14C]palmitate. The fasting plasma FFA concentration was elevated in obese subjects (793 ± 43 vs. 642 ± 39 μmol/l; P < 0.01) and was associated with an increased basal rate of plasma FFA turnover, FFA oxidation, and nonoxidative FFA disposal, i.e., reesterification (all P < 0.01). Suppression of plasma FFA turnover by physiological increments in plasma insulin was impaired in obese compared with lean subjects. However, plasma FFA turnover expressed per kilogram fat mass was normally suppressed by insulin in obese subjects. Although insulin suppressed plasma FFA oxidation to the same extent in lean and obese subjects, inhibition of total lipid oxidation by insulin was impaired in the obese group. Obese subjects had an enhanced basal rate of nonoxidative FFA disposal, which was suppressed less by physiological increments in plasma insulin compared with lean controls. Therefore, we conclude that 1) lipolysis in uncomplicated obesity is normally sensitive to insulin; the enhanced FFA flux is simply a consequence of the increased fat mass. 2) Nonoxidative FFA disposal expressed per lean body mass is enhanced in obese subjects and correlates with the increase in plasma FFA concentration and fat mass. 3) Enhanced oxidation of intracellular lipids contributes to the enhanced rate of total lipid oxidation in obese subjects.

Original languageEnglish (US)
Pages (from-to)E79-E84
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume263
Issue number1 26-1
DOIs
StatePublished - 1992
Externally publishedYes

Keywords

  • glucose

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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