Metabolomic analysis reveals altered skeletal muscle amino acid and fatty acid handling in obese humans

Obesity (Silver Spring). 2015 May;23(5):981-988. doi: 10.1002/oby.21046. Epub 2015 Apr 10.

Abstract

Objective: Investigate the effects of obesity and high-fat diet (HFD) exposure on fatty acid oxidation and TCA cycle intermediates and amino acids in skeletal muscle to better characterize energy metabolism.

Methods: Plasma and skeletal muscle metabolomic profiles were measured from lean and obese males before and after a 5-day HFD in the 4 h postprandial condition.

Results: At both time points, plasma short-chain acylcarnitine species (SCAC) were higher in the obese subjects, while the amino acids glycine, histidine, methionine, and citrulline were lower in skeletal muscle of obese subjects. Skeletal muscle medium-chain acylcarnitines (MCAC) C6, C8, C10:2, C10:1, C10, and C12:1 increased in obese subjects, but decreased in lean subjects, from pre- to post-HFD. Plasma content of C10:1 was also decreased in the lean but increased in the obese subjects from pre- to post-HFD. CD36 increased from pre- to post-HFD in obese but not lean subjects.

Conclusions: Lower skeletal muscle amino acid content and accumulation of plasma SCAC in obese subjects could reflect increased anaplerosis for TCA cycle intermediates, while accumulation of MCAC suggests limitations in β-oxidation. These measures may be important markers of or contributors to dysregulated metabolism observed in skeletal muscle of obese humans.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Amino Acids / metabolism*
  • Carnitine / analogs & derivatives
  • Carnitine / blood
  • Diet, High-Fat
  • Energy Metabolism / physiology
  • Fatty Acids / metabolism*
  • Humans
  • Lipid Metabolism / physiology
  • Male
  • Metabolomics*
  • Muscle, Skeletal / metabolism*
  • Obesity / metabolism*
  • Obesity / physiopathology
  • Oxidation-Reduction
  • Postprandial Period

Substances

  • Amino Acids
  • Fatty Acids
  • acylcarnitine
  • Carnitine