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A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease
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 r...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537762/ https://www.ncbi.nlm.nih.gov/pubmed/28640216 http://dx.doi.org/10.3390/nu9070642 |
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author | Goffredo, Martina Santoro, Nicola Tricò, Domenico Giannini, Cosimo D’Adamo, Ebe Zhao, Hongyu Peng, Gang Yu, Xiaoqing Lam, Tukiet T. Pierpont, Bridget Caprio, Sonia Herzog, Raimund I. |
author_facet | Goffredo, Martina Santoro, Nicola Tricò, Domenico Giannini, Cosimo D’Adamo, Ebe Zhao, Hongyu Peng, Gang Yu, Xiaoqing Lam, Tukiet T. Pierpont, Bridget Caprio, Sonia Herzog, Raimund I. |
author_sort | Goffredo, Martina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5537762 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-55377622017-08-04 A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease Goffredo, Martina Santoro, Nicola Tricò, Domenico Giannini, Cosimo D’Adamo, Ebe Zhao, Hongyu Peng, Gang Yu, Xiaoqing Lam, Tukiet T. Pierpont, Bridget Caprio, Sonia Herzog, Raimund I. Nutrients Article 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. MDPI 2017-06-22 /pmc/articles/PMC5537762/ /pubmed/28640216 http://dx.doi.org/10.3390/nu9070642 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Goffredo, Martina Santoro, Nicola Tricò, Domenico Giannini, Cosimo D’Adamo, Ebe Zhao, Hongyu Peng, Gang Yu, Xiaoqing Lam, Tukiet T. Pierpont, Bridget Caprio, Sonia Herzog, Raimund I. A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease |
title | A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease |
title_full | A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease |
title_fullStr | A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease |
title_full_unstemmed | A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease |
title_short | A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease |
title_sort | branched-chain amino acid-related metabolic signature characterizes obese adolescents with non-alcoholic fatty liver disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537762/ https://www.ncbi.nlm.nih.gov/pubmed/28640216 http://dx.doi.org/10.3390/nu9070642 |
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