Circulating lysophosphatidylcholines are markers of a metabolically benign nonalcoholic fatty liver.
Circulating lysophosphatidylcholines are markers of a metabolically benign nonalcoholic fatty liver.
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DOI：
10.2337/dc12-1760
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发表时间：
2013-08
期刊：
影响因子：
16.2
通讯作者：
Stefan N
中科院分区：
文献类型：
--
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
非酒精性脂肪肝（NAFL）被认为是导致胰岛素抵抗及其代谢并发症的原因。然而，一些NAFL患者仍然对胰岛素敏感。NAFL患者易发生胰岛素抵抗的机制尚不清楚。我们通过应用代谢组学方法研究了代谢良性和恶性NAFL的循环标志物和机制。在9个月的生活方式干预之前和之后，分析了20名胰岛素敏感和20名胰岛素抵抗的NAFL受试者的血浆中总共265种代谢物。然后在17名无NAFL的受试者和29名有肝组织样本的受试者的血浆中检测相关血浆代谢物与胰岛素敏感性的关系。通过包括支链氨基酸亮氨酸和异亮氨酸、鸟氨酸、酰基肉毒碱C3：0-、C16：0-和C18：0-肉毒碱以及溶血磷脂酰胆碱（lyso-PC）C16：0的代谢物模式实现了胰岛素敏感性与胰岛素抵抗NAFL组的最佳分离（ROC曲线下面积，基线时为0.77 [P = 0.00023]，随访时为0.80 [P = 0.000019]）。在个体代谢物中，与胰岛素抵抗受试者相比，在基线（P = 0.0039）和随访（P = 0.001）时，胰岛素敏感受试者的溶血PC C16：0水平主要较高。在非NAFL组中，在胰岛素敏感和胰岛素抵抗受试者之间没有发现溶血PC C16：0水平的差异，并且这些关系在来自具有肝组织样本的受试者的血浆中复制。从血浆代谢组学模式来看，特别是溶血PC能够在人体中将代谢良性与恶性NAFL分开，并可能突出脂肪肝诱导的胰岛素抵抗发病机制中的重要途径。
Nonalcoholic fatty liver (NAFL) is thought to contribute to insulin resistance and its metabolic complications. However, some individuals with NAFL remain insulin sensitive. Mechanisms involved in the susceptibility to develop insulin resistance in humans with NAFL are largely unknown. We investigated circulating markers and mechanisms of a metabolically benign and malignant NAFL by applying a metabolomic approach. A total of 265 metabolites were analyzed before and after a 9-month lifestyle intervention in plasma from 20 insulin-sensitive and 20 insulin-resistant subjects with NAFL. The relevant plasma metabolites were then tested for relationships with insulin sensitivity in 17 subjects without NAFL and in plasma from 29 subjects with liver tissue samples. The best separation of the insulin-sensitive from the insulin-resistant NAFL group was achieved by a metabolite pattern including the branched-chain amino acids leucine and isoleucine, ornithine, the acylcarnitines C3:0-, C16:0-, and C18:0-carnitine, and lysophosphatidylcholine (lyso-PC) C16:0 (area under the ROC curve, 0.77 [P = 0.00023] at baseline and 0.80 [P = 0.000019] at follow-up). Among the individual metabolites, predominantly higher levels of lyso-PC C16:0, both at baseline (P = 0.0039) and at follow-up (P = 0.001), were found in the insulin-sensitive compared with the insulin-resistant subjects. In the non-NAFL groups, no differences in lyso-PC C16:0 levels were found between the insulin-sensitive and insulin-resistant subjects, and these relationships were replicated in plasma from subjects with liver tissue samples. From a plasma metabolomic pattern, particularly lyso-PCs are able to separate metabolically benign from malignant NAFL in humans and may highlight important pathways in the pathogenesis of fatty liver–induced insulin resistance.