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 language | English (US) |
|---|---|
| Pages (from-to) | 256-267 |
| Number of pages | 12 |
| Journal | American Journal of Clinical Nutrition |
| Volume | 102 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 1 2015 |
| Externally published | Yes |
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Keywords
- Acylcarnitines
- Amino acids
- Carbohydrates
- Lipids
- Nucleotides
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Nutrition and Dietetics
Cite this
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 journal › Article
}
TY - JOUR
T1 - Global metabolomic profiling targeting childhood obesity in the Hispanic population
AU - Butte, Nancy F.
AU - Liu, Yan
AU - Zakeri, Issa F.
AU - Mohney, Robert P.
AU - Mehta, Nitesh
AU - Voruganti, V. Saroja
AU - Göring, Harald
AU - Cole, Shelley A.
AU - Comuzzie, Anthony G.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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.
AB - 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.
KW - Acylcarnitines
KW - Amino acids
KW - Carbohydrates
KW - Lipids
KW - Nucleotides
UR - http://www.scopus.com/inward/record.url?scp=84938686905&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938686905&partnerID=8YFLogxK
U2 - 10.3945/ajcn.115.111872
DO - 10.3945/ajcn.115.111872
M3 - Article
C2 - 26085512
AN - SCOPUS:84938686905
VL - 102
SP - 256
EP - 267
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
SN - 0002-9165
IS - 2
ER -