title: Metabolomic profiling of fatty acid and amino acid metabolism in youth with obesity and type 2 diabetes: evidence for enhanced mitochondrial oxidation.
abstract: OBJECTIVE
  We compared acylcarnitine (AcylCN) species, common amino acid and fat oxidation (FOX) byproducts, and plasma amino acids in normal weight (NW; n = 39), obese (OB; n = 64), and type 2 diabetic (n = 17) adolescents.
  
  
  METHODS
  Fasting plasma was analyzed by tandem mass spectrometry, body composition by dual energy X-ray absorptiometry and computed tomography, and total-body lipolysis and substrate oxidation by [(2)H(5)]glycerol and indirect calorimetry, respectively. In vivo insulin sensitivity (IS) was assessed with a 3-h hyperinsulinemic-euglycemic clamp.
  
  
  RESULTS
  Long-chain AcylCNs (C18:2-CN to C14:0-CN) were similar among the three groups. Medium- to short-chain AcylCNs (except C8 and C10) were significantly lower in type 2 diabetes compared with NW, and when compared with OB, C2-, C6-, and C10-CN were lower. Amino acid concentrations were lower in type 2 diabetes compared with NW. Fasting lipolysis and FOX were higher in OB and type 2 diabetes compared with NW, and the negative association of FOX to C10:1 disappeared after controlling for adiposity, Tanner stage, and sex. IS was lower in OB and type 2 diabetes with positive associations between IS and arginine, histidine, and serine after adjusting for adiposity, Tanner stage, and sex.
  
  
  CONCLUSIONS
  These metabolomics results, together with the increased rates of in vivo FOX, are not supportive of defective fatty acid or amino acid metabolism in obesity and type 2 diabetes in youth. Such observations are consistent with early adaptive metabolic plasticity in youth, which over time-with continued obesity and aging-may become dysfunctional, as observed in adults.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Mihalik
authors.forename: Sara F
authors.initials: SF
authors.lastname: Michaliszyn
authors.forename: Javier
authors.initials: J
authors.lastname: de las Heras
authors.forename: Fida
authors.initials: F
authors.lastname: Bacha
authors.forename: SoJung
authors.initials: S
authors.lastname: Lee
authors.forename: Donald H
authors.initials: DH
authors.lastname: Chace
authors.forename: Victor R
authors.initials: VR
authors.lastname: DeJesus
authors.forename: Jerry
authors.initials: J
authors.lastname: Vockley
authors.forename: Silva A
authors.initials: SA
authors.lastname: Arslanian
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D000596:Amino Acids / Q000378:metabolism*; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000196:embryology*; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009765:Obesity / Q000196:embryology*
chemical_list: D000596:Amino Acids; D005227:Fatty Acids; C116917:acylcarnitine; D002331:Carnitine