title: Global metabolomic profiling targeting childhood obesity in the Hispanic population.
abstract: BACKGROUND
  Metabolomics may unravel important biological pathways involved in the pathophysiology of childhood obesity.
  
  
  OBJECTIVE
  We aimed to 1) identify metabolites that differ significantly between nonobese and obese Hispanic children; 2) collapse metabolites into principal components (PCs) associated with obesity and metabolic risk, specifically hyperinsulinemia, hypertriglyceridemia, hyperleptinemia, and hyperuricemia; and 3) identify metabolites associated with energy expenditure and fat oxidation.
  
  
  METHODS
  This trial was a cross-sectional observational study of metabolomics by using gas chromatography-mass spectrometry and ultrahigh-performance liquid chromatography-tandem mass spectrometry analyses performed on fasting plasma samples from 353 nonobese and 450 obese Hispanic children.
  
  
  RESULTS
  Branched-chained amino acids (BCAAs) (Leu, Ile, and Val) and their catabolites, propionylcarnitine and butyrylcarnitine, were significantly elevated in obese children. Strikingly lower lysolipids and dicarboxylated fatty acids were seen in obese children. Steroid derivatives were markedly higher in obese children as were markers of inflammation and oxidative stress. PC6 (BCAAs and aromatic AAs) and PC10 (asparagine, glycine, and serine) made the largest contributions to body mass index, and PC10 and PC12 (acylcarnitines) made the largest contributions to adiposity. Metabolic risk factors and total energy expenditure were associated with PC6, PC9 (AA and tricarboxylic acid cycle metabolites), and PC10. Fat oxidation was inversely related to PC8 (lysolipids) and positively related to PC16 (acylcarnitines).
  
  
  CONCLUSIONS
  Global metabolomic profiling in nonobese and obese children replicates the increased BCAA and acylcarnitine catabolism and changes in nucleotides, lysolipids, and inflammation markers seen in obese adults; however, a strong signature of reduced fatty acid catabolism and increased steroid derivatives may be unique to obese children. Metabolic flexibility in fuel use observed in obese children may occur through the activation of alternative intermediary pathways. Insulin resistance, hyperleptinemia, hypertriglyceridemia, hyperuricemia, and oxidative stress and inflammation evident in obese children are associated with distinct metabolomic profiles.
authors.affiliation: USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX; nbutte@bcm.edu.
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Butte
authors.affiliation: USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Biostatistics, Drexel University, Philadelphia, PA;
authors.forename: Issa F
authors.initials: IF
authors.lastname: Zakeri
authors.affiliation: Metabolon Inc., Durham, NC;
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mohney
authors.affiliation: USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX;
authors.forename: Nitesh
authors.initials: N
authors.lastname: Mehta
authors.affiliation: Department of Nutrition and University of North Carolina at Chapel Hill Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC; and.
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Harald
authors.initials: H
authors.lastname: Göring
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004734:Energy Metabolism; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000208:ethnology / Q000209:etiology*; D055442:Metabolome; D050177:Overweight / Q000097:blood / Q000208:ethnology / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress; D063766:Pediatric Obesity / Q000097:blood / Q000208:ethnology / Q000378:metabolism* / Q000503:physiopathology; D025341:Principal Component Analysis; D012307:Risk Factors; D013781:Texas / Q000453:epidemiology
chemical_list: D015415:Biomarkers
keywords: acylcarnitines; amino acids; carbohydrates; lipids; nucleotides