A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease.
A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease.
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DOI：
10.3390/nu9070642
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发表时间：
2017-06-22
期刊：
影响因子：
5.9
通讯作者：
Herzog RI
中科院分区：
文献类型：
--
作者：
Goffredo M;Santoro N;Tricò D;Giannini C;D'Adamo E;Zhao H;Peng G;Yu X;Lam TT;Pierpont B;Caprio S;Herzog RI
包括支链氨基酸（BCAA）在内的几种代谢途径的失调与成人的非酒精性脂肪肝（NAFLD）和胰岛素抵抗有关，而青年研究报告了相互矛盾的结果。我们探讨了肥胖青少年NAFLD患者的代谢组学特征是否与肥胖和胰岛素抵抗无关，与氨基酸和脂质代谢紊乱一致。通过靶向代谢组学方法测量了78名患有（n = 30）或未患有（n = 48）NAFLD的肥胖青少年的180种血浆代谢物，这些青少年通过磁共振成像（MRI）进行评估。所有受试者均接受口服葡萄糖耐量试验，患者亚组在2.2 ± 0.8年随访后接受两步高胰岛素-正常血糖钳夹和/或第二次MRI。校正混杂因素后，NAFLD青少年的血浆缬氨酸（p = 0.02）、异亮氨酸（p = 0.03）、色氨酸（p = 0.02）和赖氨酸（p = 0.02）水平较高。循环支链氨基酸与外周和肝脏胰岛素敏感性呈负相关。此外，较高的基线缬氨酸水平预测随访时肝脂肪含量（HFF）增加（p = 0.01）。这些结果表明，BCAA代谢失调是肥胖青少年NAFLD的特征，与肥胖和胰岛素抵抗无关，并预测肝脏脂肪含量随时间增加。
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.
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影响因子：
4.2
作者：
Metges, CC
通讯作者：
Metges, CC
影响因子：
3.7
作者：
Mascaro J;Asner GP;Knapp DE;Kennedy-Bowdoin T;Martin RE;Anderson C;Higgins M;Chadwick KD
通讯作者：
Chadwick KD
影响因子：
16.2
作者：
Lehmann R;Franken H;Dammeier S;Rosenbaum L;Kantartzis K;Peter A;Zell A;Adam P;Li J;Xu G;Königsrainer A;Machann J;Schick F;Hrabé de Angelis M;Schwab M;Staiger H;Schleicher E;Gastaldelli A;Fritsche A;Häring HU;Stefan N
通讯作者：
Stefan N
影响因子：
16.2
作者：
Lee, C. Christine;Watkins, Steve M.;Hanley, Anthony J.
通讯作者：
Hanley, Anthony J.
影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH