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Nutrients 2017, 9(7), 642; doi:10.3390/nu9070642

A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease

1
Department of Pediatrics, Yale University School of Medicine, 330 Cedar Street, P.O. Box 208064, New Haven, CT 06520, USA
2
Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, P.O. Box 208020, New Haven, CT 06520, USA
3
Department of Clinical and Experimental Medicine, University of Pisa, Pisa PI 56126, Italy
4
Department of Pediatrics, University of Chieti, Chieti CH 66100, Italy
5
Yale School of Public Health, New Haven, CT 06520, USA
6
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA
These authors contributed equally to the manuscript.
*
Authors to whom correspondence should be addressed.
Received: 1 May 2017 / Revised: 2 June 2017 / Accepted: 19 June 2017 / Published: 22 June 2017
(This article belongs to the Special Issue Nutrition and Non-alcoholic Fatty Liver Disease)
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Abstract

Dysregulation of several metabolite pathways, including branched-chain amino acids (BCAAs), are associated with Non-Alcoholic Fatty Liver Disease (NAFLD) and insulin resistance in adults, while studies in youth reported conflicting results. We explored whether, independently of obesity and insulin resistance, obese adolescents with NAFLD display a metabolomic signature consistent with disturbances in amino acid and lipid metabolism. A total of 180 plasma metabolites were measured by a targeted metabolomic approach in 78 obese adolescents with (n = 30) or without (n = 48) NAFLD assessed by magnetic resonance imaging (MRI). All subjects underwent an oral glucose tolerance test and subsets of patients underwent a two-step hyperinsulinemic-euglycemic clamp and/or a second MRI after a 2.2 ± 0.8-year follow-up. Adolescents with NAFLD had higher plasma levels of valine (p = 0.02), isoleucine (p = 0.03), tryptophan (p = 0.02), and lysine (p = 0.02) after adjustment for confounding factors. Circulating BCAAs were negatively correlated with peripheral and hepatic insulin sensitivity. Furthermore, higher baseline valine levels predicted an increase in hepatic fat content (HFF) at follow-up (p = 0.01). These results indicate that a dysregulation of BCAA metabolism characterizes obese adolescents with NAFLD independently of obesity and insulin resistance and predict an increase in hepatic fat content over time. View Full-Text
Keywords: metabolomics; youth; branched chain amino acids; insulin resistance; nonalcoholic fatty liver disease; obesity metabolomics; youth; branched chain amino acids; insulin resistance; nonalcoholic fatty liver disease; obesity
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Goffredo, M.; Santoro, N.; Tricò, D.; Giannini, C.; D’Adamo, E.; Zhao, H.; Peng, G.; Yu, X.; Lam, T.T.; Pierpont, B.; Caprio, S.; Herzog, R.I. A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease. Nutrients 2017, 9, 642.

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