Global metabolomic profiling targeting childhood obesity in the Hispanic population

Nancy F. Butte, Yan Liu, Issa F. Zakeri, Robert P. Mohney, Nitesh Mehta, V. Saroja Voruganti, Harald Göring, Shelley A. Cole, Anthony G. Comuzzie

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Background: Metabolomics may unravel important biological pathways involved in the pathophysiology of childhood obesity. Objectives: 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. Design: 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.

Original languageEnglish (US)
Pages (from-to)256-267
Number of pages12
JournalAmerican Journal of Clinical Nutrition
Volume102
Issue number2
DOIs
StatePublished - Aug 1 2015
Externally publishedYes

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Metabolomics
Pediatric Obesity
Hispanic Americans
Population
Hyperuricemia
propionylcarnitine
Hypertriglyceridemia
Inflammation
Energy Metabolism
Oxidative Stress
Fatty Acids
Fats
Steroids
Amino Acids
Aromatic Amino Acids
Citric Acid Cycle
Asparagine
Adiposity
Hyperinsulinism
Tandem Mass Spectrometry

Keywords

  • Acylcarnitines
  • Amino acids
  • Carbohydrates
  • Lipids
  • Nucleotides

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Butte, N. F., Liu, Y., Zakeri, I. F., Mohney, R. P., Mehta, N., Voruganti, V. S., ... Comuzzie, A. G. (2015). Global metabolomic profiling targeting childhood obesity in the Hispanic population. American Journal of Clinical Nutrition, 102(2), 256-267. https://doi.org/10.3945/ajcn.115.111872

Global metabolomic profiling targeting childhood obesity in the Hispanic population. / Butte, Nancy F.; Liu, Yan; Zakeri, Issa F.; Mohney, Robert P.; Mehta, Nitesh; Voruganti, V. Saroja; Göring, Harald; Cole, Shelley A.; Comuzzie, Anthony G.

In: American Journal of Clinical Nutrition, Vol. 102, No. 2, 01.08.2015, p. 256-267.

Research output: Contribution to journalArticle

Butte, NF, Liu, Y, Zakeri, IF, Mohney, RP, Mehta, N, Voruganti, VS, Göring, H, Cole, SA & Comuzzie, AG 2015, 'Global metabolomic profiling targeting childhood obesity in the Hispanic population', American Journal of Clinical Nutrition, vol. 102, no. 2, pp. 256-267. https://doi.org/10.3945/ajcn.115.111872
Butte, Nancy F. ; Liu, Yan ; Zakeri, Issa F. ; Mohney, Robert P. ; Mehta, Nitesh ; Voruganti, V. Saroja ; Göring, Harald ; Cole, Shelley A. ; Comuzzie, Anthony G. / Global metabolomic profiling targeting childhood obesity in the Hispanic population. In: American Journal of Clinical Nutrition. 2015 ; Vol. 102, No. 2. pp. 256-267.
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