title: Enhanced skeletal muscle lipid oxidative efficiency in insulin-resistant vs insulin-sensitive nondiabetic, nonobese humans.
abstract: BACKGROUND
  Skeletal muscle insulin resistance is proposed to result from impaired skeletal muscle lipid oxidative capacity. However, there is no evidence indicating that muscle lipid oxidative capacity is impaired in healthy otherwise insulin-resistant individuals.
  
  
  OBJECTIVE
  The objective of the study was to assess muscle lipid oxidative capacity in young, nonobese, glucose-tolerant, insulin-resistant vs insulin-sensitive individuals.
  
  
  METHODS
  In 13 insulin-sensitive [by Matsuda index (MI) (22.6 ± 0.6 [SE] kg/m(2)); 23 ± 1 years; MI 5.9 ± 0.1] and 13 insulin-resistant (23.2 ± 0.6 kg/m(2); 23 ± 3 years; MI 2.2 ± 0.1) volunteers, skeletal muscle biopsy, blood extraction before and after an oral glucose load, and dual-energy x-ray absorptiometry were performed.
  
  
  METHODS
  Skeletal muscle mitochondrial to nuclear DNA ratio, oxidative phosphorylation protein content, and citrate synthase and β-hydroxyacyl-CoA dehydrogenase activities were assessed. Muscle lipids and palmitate oxidation ((14)CO2 and (14)C-acid soluble metabolites production) at 4 [1-(14)C]palmitate concentrations (45-520 μM) were also measured.
  
  
  RESULTS
  None of the muscle mitochondrial measures showed differences between groups, except for a higher complex V protein content in insulin-resistant vs insulin-sensitive volunteers (3.5 ± 0.4 vs 2.2 ± 0.4; P = .05). Muscle ceramide content was significantly increased in insulin-resistant vs insulin-sensitive individuals (P = .04). Total palmitate oxidation showed a similar concentration-dependent response in both groups (P = .69). However, lipid oxidative efficiency (CO2 to (14)C-acid soluble metabolites ratio) was enhanced in insulin-resistant vs insulin-sensitive individuals, particularly at the highest palmitate concentration (0.24 ± 0.04 vs 0.12 ± 0.02; P = .02).
  
  
  CONCLUSIONS
  We found no evidence of impaired muscle mitochondrial oxidative capacity in young, nonobese, glucose-tolerant, otherwise insulin-resistant vs insulin-sensitive individuals. Enhanced muscle lipid oxidative efficiency in insulin resistance could be a potential mechanism to prevent further lipotoxicity.
authors: Department of Nutrition, Diabetes, and Metabolism, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago, Chile. jgalgani@uc.cl
authors: Jose E
authors: JE
authors: Galgani
authors: Karla
authors: K
authors: Vasquez
authors: Guillermo
authors: G
authors: Watkins
authors: Aude
authors: A
authors: Dupuy
authors: Justine
authors: J
authors: Bertrand-Michel
authors: Thierry
authors: T
authors: Levade
authors: Cedric
authors: C
authors: Moro
mesh_terms: D000293:Adolescent; D000328:Adult; D004526:Efficiency; D005260:Female; D006801:Humans; D056865:Ideal Body Weight / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D015854:Up-Regulation; D055815:Young Adult