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Title: Global metabolomic profiling targeting childhood obesity in the Hispanic population

Author
item BUTTE, NANCY - Children'S Nutrition Research Center (CNRC)
item LIU, YAN - Children'S Nutrition Research Center (CNRC)
item ZAKERI, ISSA - Drexel University
item MOHNEY, ROBERT - Metabolon, Inc
item MEHTA, NITESH - Children'S Nutrition Research Center (CNRC)
item VORUGANTI, V - University Of North Carolina
item GORING, HARALD - Texas Biomedical Institute
item COLE, SHELLEY - Texas Biomedical Institute
item COMUZZIE, ANTHONY - Texas Biomedical Institute

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/18/2015
Publication Date: 6/17/2015
Citation: Butte, N.F., Liu, Y., Zakeri, I.F., Mohney, R.P., Mehta, N., Voruganti, V.S., Goring, H., Cole, S.A., Comuzzie, A.G. 2015. Global metabolomic profiling targeting childhood obesity in the Hispanic population. American Journal of Clinical Nutrition. 10.3945.

Interpretive Summary: Metabolomics may unravel important biological pathways involved in the pathophysiology of childhood obesity. Metabolomic profiling was used to identify metabolites associated with childhood obesity, metabolic risk factors, and energy expenditure and fat oxidation in Hispanic children. Gas chromatography–mass spectrometry and ultrahigh-performance liquid chromatography–tandem mass spectrometry analyses were performed on fasting plasma samples from 353 nonobese and 450 obese Hispanic children. Striking differences were seen in the obese children: higher branched-chained amino acids and their catabolites, propionylcarnitine and butyrylcarnitine; lower lysolipids and dicarboxylated fatty acids; and higher steroid derivatives. Metabolomic profiles indicative of insulin resistance, hyperleptinemia, hypertriglyceridemia, hyperuricemia, and oxidative stress and inflammation were observed in the obese children. This information will be useful for those conducting research associated with childhood obesity.

Technical Abstract: Metabolomics may unravel important biological pathways involved in the pathophysiology of childhood obesity. 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. 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. 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). 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.