Muscle sphingolipids during rest and exercise: a C18:0 signature for insulin resistance in humans

Diabetologia. 2016 Apr;59(4):785-98. doi: 10.1007/s00125-015-3850-y. Epub 2016 Jan 6.


Aims/hypotheses: Ceramides and other sphingolipids comprise a family of lipid molecules that accumulate in skeletal muscle and promote insulin resistance. Chronic endurance exercise training decreases muscle ceramides and other sphingolipids, but less is known about the effects of a single bout of exercise.

Methods: We measured basal relationships and the effect of acute exercise (1.5 h at 50% [Formula: see text]) and recovery on muscle sphingolipid content in obese volunteers, endurance trained athletes and individuals with type 2 diabetes.

Results: Muscle C18:0 ceramide (p = 0.029), dihydroceramide (p = 0.06) and glucosylceramide (p = 0.03) species were inversely related to insulin sensitivity without differences in total ceramide, dihydroceramide, and glucosylceramide concentration. Muscle C18:0 dihydroceramide correlated with markers of muscle inflammation (p = 0.04). Transcription of genes encoding sphingolipid synthesis enzymes was higher in athletes, suggesting an increased capacity for sphingolipid synthesis. The total concentration of muscle ceramides and sphingolipids increased during exercise and then decreased after recovery, during which time ceramide levels reduced to significantly below basal levels.

Conclusions/interpretation: These data suggest ceramide and other sphingolipids containing stearate (18:0) are uniquely related to insulin resistance in skeletal muscle. Recovery from an exercise bout decreased muscle ceramide concentration; this may represent a mechanism promoting the insulin-sensitising effects of acute exercise.

Keywords: Athlete’s paradox; Insulin sensitivity; Lipid composition.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Blotting, Western
  • Ceramides / metabolism
  • Exercise / physiology*
  • Humans
  • Insulin Resistance / physiology
  • Muscle, Skeletal / metabolism*
  • Rest / physiology*
  • Sphingolipids / metabolism*


  • Ceramides
  • Sphingolipids