Altered body composition and energy expenditure but normal glucose tolerance among humans with a long-chain fatty acid oxidation disorder

Am J Physiol Endocrinol Metab. 2013 Nov 15;305(10):E1299-308. doi: 10.1152/ajpendo.00225.2013. Epub 2013 Sep 24.


The development of insulin resistance has been associated with impaired mitochondrial fatty acid oxidation (FAO), but the exact relationship between FAO capacity and glucose metabolism continues to be debated. To address this controversy, patients with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) deficiency underwent an oral glucose tolerance test (OGTT) and measurement of energy expenditure, body composition, and plasma metabolites. Compared with controls, patients with LCHAD deficiency had a trend toward higher total body fat and extramyocellular lipid deposition but similar levels of intramyocelluar and intrahepatic lipids. Resting energy expenditure was similar between the groups, but respiratory quotient was higher and total energy expenditure was lower in LCHAD-deficient patients compared with controls. High-molecular-weight (HMW) adiponectin levels were lower and plasma long-chain acylcarnitines were higher among LCHAD-deficient patients. Fasting and post-OGTT levels of glucose, insulin, and ghrelin, along with estimates of insulin sensitivity, were the same between the groups. Despite decreased capacity for FAO, lower total energy expenditure and plasma HMW adiponectin, and increased plasma acylcarnitines, LCHAD-deficient patients exhibited normal glucose tolerance. These data suggest that inhibition of the FAO pathway in humans is not sufficient to induce insulin resistance.

Keywords: acylcarnitines; long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl-CoA Dehydrogenase, Long-Chain / blood
  • Acyl-CoA Dehydrogenase, Long-Chain / deficiency*
  • Acyl-CoA Dehydrogenase, Long-Chain / metabolism
  • Adolescent
  • Blood Glucose / metabolism*
  • Body Composition*
  • Case-Control Studies
  • Child
  • Energy Metabolism / physiology*
  • Female
  • Glucose Tolerance Test
  • Humans
  • Insulin Resistance
  • Lipid Metabolism, Inborn Errors / blood
  • Lipid Metabolism, Inborn Errors / metabolism*
  • Magnetic Resonance Imaging
  • Male
  • Oxidation-Reduction


  • Blood Glucose
  • Acyl-CoA Dehydrogenase, Long-Chain

Supplementary concepts

  • Long-chain acyl-CoA dehydrogenase deficiency