Serum aromatic and branched-chain amino acids associated with NASH demonstrate divergent associations with serum lipids.
Serum aromatic and branched-chain amino acids associated with NASH demonstrate divergent associations with serum lipids.
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DOI：
10.1111/liv.14743
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Pihlajamäki J
中科院分区：
文献类型：
--
作者：
de Mello VD;Sehgal R;Männistö V;Klåvus A;Nilsson E;Perfilyev A;Kaminska D;Miao Z;Pajukanta P;Ling C;Hanhineva K;Pihlajamäki J
非酒精性脂肪性肝病（NAFLD）与多种代谢异常相关。通过应用非靶向代谢组学方法，我们旨在研究与NAFLD相关的血清代谢物谱是否与NAFLD相关的代谢危险因素相关。共研究了233例接受减肥手术的受试者（平均值± SD：48.3 ± 9.3岁; BMI：43.1 ± 5.4 kg/m2; 64例男性）。在这些参与者中，164名肝脏组织学检查结果可分为正常肝脏（n = 79）、单纯性脂肪变性（SS，n = 40）或非酒精性脂肪性肝炎（NASH，n = 45）。与具有正常表型的那些相比，在具有NASH的那些中具有更高水平的所鉴定的空腹血清代谢物是芳香族氨基酸（AAA：色氨酸、酪氨酸和苯丙氨酸）、支链氨基酸（BCAA：亮氨酸和异亮氨酸）、磷脂酰胆碱（PC（16：0/16：1））和尿苷（所有FDRP < 0.05）。与患有SS的那些相比，患有NASH的那些中仅色氨酸显著更高（FDRP < 0.05）。只有色氨酸和酪氨酸与血清总胆固醇和低密度脂蛋白胆固醇呈正相关（FDRP < 0.1），因此，在mRNA表达水平上与肝脏LDLR呈正相关。此外，色氨酸是与已知在NASH患者中差异甲基化的CpG位点的肝脏DNA甲基化相关的单一AA。我们发现NASH相关的AAA和BCAA的血清水平与血脂表现出不同的相关性。色氨酸与LDL-c的特异性相关性可能是由于影响LDLR mRNA表达的分子事件和肝脏中NASH相关基因甲基化。
Non‐alcoholic fatty liver disease (NAFLD) has been associated with multiple metabolic abnormalities. By applying a non‐targeted metabolomics approach, we aimed at investigating whether serum metabolite profile that associates with NAFLD would differ in its association with NAFLD‐related metabolic risk factors. A total of 233 subjects (mean ± SD: 48.3 ± 9.3 years old; BMI: 43.1 ± 5.4 kg/m2; 64 male) undergoing bariatric surgery were studied. Of these participants, 164 with liver histology could be classified as normal liver (n = 79), simple steatosis (SS, n = 40) or non‐alcoholic steatohepatitis (NASH, n = 45). Among the identified fasting serum metabolites with higher levels in those with NASH when compared to those with normal phenotype were the aromatic amino acids (AAAs: tryptophan, tyrosine and phenylalanine), the branched‐chain amino acids (BCAAs: leucine and isoleucine), a phosphatidylcholine (PC(16:0/16:1)) and uridine (all FDRp < 0.05). Only tryptophan was significantly higher in those with NASH compared to those with SS (FDRp < 0.05). Only the AAAs tryptophan and tyrosine correlated positively with serum total and LDL cholesterol (FDRp < 0.1), and accordingly, with liver LDLR at mRNA expression level. In addition, tryptophan was the single AA associated with liver DNA methylation of CpG sites known to be differentially methylated in those with NASH. We found that serum levels of the NASH‐related AAAs and BCAAs demonstrate divergent associations with serum lipids. The specific correlation of tryptophan with LDL‐c may result from the molecular events affecting LDLR mRNA expression and NASH‐associated methylation of genes in the liver.
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影响因子：
5.9
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
通讯作者：
Herzog RI
影响因子：
4.2
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
14.9
作者：
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通讯作者：
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影响因子：
29
作者：
Min HK;Kapoor A;Fuchs M;Mirshahi F;Zhou H;Maher J;Kellum J;Warnick R;Contos MJ;Sanyal AJ
通讯作者：
Sanyal AJ