title: Skeletal muscle and plasma lipidomic signatures of insulin resistance and overweight/obesity in humans.
abstract: OBJECTIVE
  Alterations in lipids in muscle and plasma have been documented in insulin-resistant people with obesity. Whether these lipid alterations are a reflection of insulin resistance or obesity remains unclear.
  
  
  METHODS
  Nondiabetic sedentary individuals not treated with lipid-lowering medications were studied (n = 51). Subjects with body mass index (BMI) > 25 kg/m(2) (n = 28) were stratified based on median glucose infusion rate during a hyperinsulinemic-euglycemic clamp into insulin-sensitive and insulin-resistant groups (above and below median, obesity/insulin-sensitive and obesity/insulin-resistant, respectively). Lean individuals (n = 23) served as a reference group. Lipidomics was performed in muscle and plasma by liquid chromatography electrospray ionization-tandem mass spectrometry. Pathway analysis of gene array in muscle was performed in a subset (n = 35).
  
  
  RESULTS
  In muscle, insulin resistance was characterized by higher levels of C18:0 sphingolipids, while in plasma, higher levels of diacylglycerol and cholesterol ester, and lower levels of lysophosphatidylcholine and lysoalkylphosphatidylcholine, indicated insulin resistance, irrespective of overweight/obesity. The sphingolipid metabolism gene pathway was upregulated in muscle in insulin resistance independent of obesity. An overweight/obesity lipidomic signature was only apparent in plasma, predominated by higher triacylglycerol and lower plasmalogen species.
  
  
  CONCLUSIONS
  Muscle C18:0 sphingolipids may play a role in insulin resistance independent of excess adiposity.
authors.affiliation: Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.|Faculty of Medicine, UNSW, Sydney, New South Wales, Australia.|Department of Endocrinology and Diabetes Centre, St. Vincent's Hospital, Sydney, New South Wales, Australia.
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Tonks
authors.affiliation: Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.|School of Mathematics and Statistics, UNSW, Sydney, New South Wales, Australia.
authors.forename: Adelle Cf
authors.initials: AC
authors.lastname: Coster
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Christopher
authors.affiliation: Charles Perkins Centre, School of Molecular Bioscience, School of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Rima
authors.initials: R
authors.lastname: Chaudhuri
authors.affiliation: Department of Medicine, Department of Pharmacology and Pharmacy, and Research Center of Heart, Brain, Hormone and Healthy Ageing, University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Statistics, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Johann
authors.initials: J
authors.lastname: Gagnon-Bartsch
authors.affiliation: Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.|Faculty of Medicine, UNSW, Sydney, New South Wales, Australia.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Chisholm
authors.affiliation: Charles Perkins Centre, School of Molecular Bioscience, School of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: David E
authors.initials: DE
authors.lastname: James
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
authors.affiliation: Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.|Faculty of Medicine, UNSW, Sydney, New South Wales, Australia.|Department of Endocrinology and Diabetes Centre, St. Vincent's Hospital, Sydney, New South Wales, Australia.
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Greenfield
authors.affiliation: Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.|Faculty of Medicine, UNSW, Sydney, New South Wales, Australia.
authors.forename: Dorit
authors.initials: D
authors.lastname: Samocha-Bonet
mesh_terms: D050154:Adiposity; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D002788:Cholesterol Esters / Q000097:blood; D004075:Diglycerides / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000235:genetics; D008244:Lysophosphatidylcholines / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D050177:Overweight / Q000378:metabolism*; D010955:Plasmalogens / Q000097:blood; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation
chemical_list: D002788:Cholesterol Esters; D004075:Diglycerides; D007328:Insulin; D008244:Lysophosphatidylcholines; D010955:Plasmalogens; D013107:Sphingolipids; D014280:Triglycerides; D005947:Glucose