title: Muscle sphingolipids during rest and exercise: a C18:0 signature for insulin resistance in humans.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, PO Box 6511, MS 8106, Aurora, CO, 80045, USA. Bryan.Bergman@ucdenver.edu.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Bergman
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Brozinick
authors.affiliation: Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, PO Box 6511, MS 8106, Aurora, CO, 80045, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Strauss
authors.affiliation: Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, PO Box 6511, MS 8106, Aurora, CO, 80045, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Bacon
authors.affiliation: Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, PO Box 6511, MS 8106, Aurora, CO, 80045, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Kerege
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Hai Hoang
authors.initials: HH
authors.lastname: Bui
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Phil
authors.initials: P
authors.lastname: Sanders
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Parker
authors.initials: P
authors.lastname: Siddall
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wei
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Thomas
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Ming Shang
authors.initials: MS
authors.lastname: Kuo
authors.affiliation: Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, PO Box 6511, MS 8106, Aurora, CO, 80045, USA.
authors.forename: Leigh
authors.initials: L
authors.lastname: Perreault
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002518:Ceramides / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D012146:Rest / Q000502:physiology*; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: D002518:Ceramides; D013107:Sphingolipids
keywords: Athlete’s paradox; Insulin sensitivity; Lipid composition