Plasma metabolomics identifies lipid abnormalities linked to markers of inflammation, microbial translocation, and hepatic function in HIV patients receiving protease inhibitors.
Plasma metabolomics identifies lipid abnormalities linked to markers of inflammation, microbial translocation, and hepatic function in HIV patients receiving protease inhibitors.
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DOI：
10.1186/1471-2334-13-203
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发表时间：
2013-05-04
影响因子：
3.7
通讯作者：
Gabuzda D
中科院分区：
文献类型：
--
作者：
Cassol E;Misra V;Holman A;Kamat A;Morgello S;Gabuzda D
代谢异常在接受抗逆转录病毒治疗（ART）的HIV感染者中很常见，但这些疾病的生化细节和潜在机制尚未确定。使用液相或气相色谱法和质谱法对32名接受基于蛋白酶抑制剂（PI）的ART的低最低CD 4计数（<300个细胞/ul）的HIV患者和20名健康对照进行血浆的非靶向代谢组学分析。丙型肝炎（HCV）合并感染的影响和改变脂质代谢物和炎症标志物，微生物易位和肝功能之间的关系进行了检查。使用dChip、Metaboanalyst和MSEA软件进行无监督分层聚类、主成分分析（PCA）、偏最小二乘判别分析（PLS-DA）、随机森林、途径作图和代谢物集富集分析（MSEA）。一个35-代谢物标签映射到脂质、氨基酸和核苷酸代谢，将接受基于PI的ART的晚期疾病的HIV患者与对照区分开来，而不管HCV血清状态如何（p<0.05，错误发现率（FDR）<0.1）。许多改变的脂质，包括胆汁酸、硫酸化类固醇、多不饱和脂肪酸和类花生酸，是调节代谢和炎症的核受体的配体。不同的脂质改变簇与炎症标志物（干扰素-α和白细胞介素-6）、微生物易位（脂多糖（LPS）和LPS结合蛋白）和肝功能（胆红素）相关（p<0.05）。脂质改变与非酒精性脂肪性肝病（NALFD）报告的脂质改变有很大重叠。胆汁酸增加与肝纤维化的非侵入性标志物（FIB-4、APRI和YKL-40）相关，并与线粒体功能障碍的标志物酰基肉毒碱相关。接受PI为基础的ART的HIV患者的脂质改变与炎症标志物、微生物易位和肝功能有关，这表明减弱先天免疫激活失调和肝功能障碍的治疗策略可能有利于预防和治疗HIV患者的代谢紊乱。
Metabolic abnormalities are common in HIV-infected individuals on antiretroviral therapy (ART), but the biochemical details and underlying mechanisms of these disorders have not been defined. Untargeted metabolomic profiling of plasma was performed for 32 HIV patients with low nadir CD4 counts (<300 cells/ul) on protease inhibitor (PI)-based ART and 20 healthy controls using liquid or gas chromatography and mass spectrometry. Effects of Hepatitis C (HCV) co-infection and relationships between altered lipid metabolites and markers of inflammation, microbial translocation, and hepatic function were examined. Unsupervised hierarchical clustering, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), Random forest, pathway mapping, and metabolite set enrichment analysis (MSEA) were performed using dChip, Metaboanalyst, and MSEA software. A 35-metabolite signature mapping to lipid, amino acid, and nucleotide metabolism distinguished HIV patients with advanced disease on PI-based ART from controls regardless of HCV serostatus (p<0.05, false discovery rate (FDR)<0.1). Many altered lipids, including bile acids, sulfated steroids, polyunsaturated fatty acids, and eicosanoids, were ligands of nuclear receptors that regulate metabolism and inflammation. Distinct clusters of altered lipids correlated with markers of inflammation (interferon-α and interleukin-6), microbial translocation (lipopolysaccharide (LPS) and LPS-binding protein), and hepatic function (bilirubin) (p<0.05). Lipid alterations showed substantial overlap with those reported in non-alcoholic fatty liver disease (NALFD). Increased bile acids were associated with noninvasive markers of hepatic fibrosis (FIB-4, APRI, and YKL-40) and correlated with acylcarnitines, a marker of mitochondrial dysfunction. Lipid alterations in HIV patients receiving PI-based ART are linked to markers of inflammation, microbial translocation, and hepatic function, suggesting that therapeutic strategies attenuating dysregulated innate immune activation and hepatic dysfunction may be beneficial for prevention and treatment of metabolic disorders in HIV patients.
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DOI：
10.1038/nrendo.2011.151
发表时间：
2011-09-20
期刊：
Nature reviews. Endocrinology
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.8
作者：
Blackard, Jason T.;Welge, Jeffrey A.;Sherman, Kenneth E.
通讯作者：
Sherman, Kenneth E.
DOI：
10.1111/j.1365-2362.1994.tb02185.x
发表时间：
1994-06-01
影响因子：
5.5
作者：
CONSTANS, J;PELLEGRIN, JL;CONRI, C
通讯作者：
CONRI, C
影响因子：
3.8
作者：
Carr, A
通讯作者：
Carr, A
影响因子：
13.5
作者：
Adinolfi, LE;Gambardella, M;Ruggiero, G
通讯作者：
Ruggiero, G