Comprehensive metabolomics profiling reveals common metabolic alterations underlying the four major non-communicable diseases in treated HIV infection.
Comprehensive metabolomics profiling reveals common metabolic alterations underlying the four major non-communicable diseases in treated HIV infection.
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全面的代谢组学分析揭示了治疗艾滋病毒感染者中四种主要非传染性疾病背后的常见代谢变化
DOI：
10.1016/j.ebiom.2021.103548
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发表时间：
2021-09
期刊：
影响因子：
11.1
通讯作者：
He N
中科院分区：
文献类型：
--
作者：
Ding Y;Lin H;Chen X;Zhu B;Xu X;Xu X;Shen W;Gao M;He N
艾滋病毒感染和正常衰老共享导致过早衰老和非传染性疾病（NCD）的免疫和炎症变化，但确切的病理生理学尚未发现。我们确定了治疗的艾滋病毒感染中各种NCD的共同代谢途径。我们进行了非靶向代谢组学研究，包括87名HIV阴性（-）正常对照（NC），87名HIV阳性（+）NC和148名HIV+受试者，他们仅患有一种类型的NCD，即亚临床颈动脉粥样硬化，神经认知障碍（NCI），肝纤维化（LF）和肾损害。所有HIV+受试者均受到病毒抑制。与HIV-NC相比，HIV+患者的细胞代谢出现了广泛的改变。甘油磷脂（GPL）代谢是比较中出现的唯一一种干扰途径，包括各年龄组的HIV-NC、各年龄组的HIV+ NC、HIV+ NC与HIV-NC以及每种HIV+ NCD与HIV+ NC。在HIV+ NC与HIV-NC、HIV+ LF或HIV+ NCI与HIV+ NC之间的比较中列出了D-谷氨酰胺和D-谷氨酸代谢以及丙氨酸-天冬氨酸-谷氨酸代谢。一致地，随后的分析鉴定了HIV+ NCD特异性的代谢组学指纹，包含42种代谢物，其相对丰度显示从HIV-NC到HIV+ NC，然后是HIV+ NCD的上升趋势（主要是GPL衍生的脂质介质）或下降趋势（主要是缩醛磷脂酰胆碱、缩醛磷脂酰乙醇胺和谷氨酰胺），反映了氧化应激增加的趋势。GPL代谢是将艾滋病毒与非传染性疾病联系起来的常见代谢紊乱，其次是谷氨酰胺和谷氨酸代谢。总之，我们的数据表明，上述代谢和相关代谢物是研究艾滋病毒感染中非传染性疾病病理生理学和制定治疗干预措施的潜在关键目标。国家传染病科技重大专项、国家自然科学基金、复旦大学义乌研究所、上海市卫生和计划生育委员会。
HIV infection and normal aging share immune and inflammatory changes that result in premature aging and non-communicable diseases (NCDs), but the exact pathophysiology is not yet uncovered. We identified the common metabolic pathways underlying various NCDs in treated HIV infection. We performed untargeted metabolomics including 87 HIV-negative (–) normal controls (NCs), 87 HIV-positive (+) NCs, and 148 HIV+ subjects with only one type of NCDs, namely, subclinical carotid atherosclerosis, neurocognitive impairment (NCI), liver fibrosis (LF) and renal impairment. All HIV+ subjects were virally suppressed. HIV+ patients presented widespread alterations in cellular metabolism compared to HIV– NCs. Glycerophospholipid (GPL) metabolism was the only one disturbed pathway presented in comparisons including HIV– NCs across age groups, HIV+ NCs across age groups, HIV+ NCs vs HIV– NCs and each of HIV+ NCDs vs HIV+ NCs. D-glutamine and D-glutamate metabolism and alanine-aspartate-glutamate metabolism were presented in comparisons between HIV+ NCs vs HIV– NCs, HIV+ LF or HIV+ NCI vs HIV+ NCs. Consistently, subsequent analysis identified a metabolomic fingerprint specific for HIV+ NCDs, containing 42 metabolites whose relative abundance showed either an upward (mainly GPL-derived lipid mediators) or a downward trend (mainly plasmalogen phosphatidylcholines, plasmalogen phosphatidylethanolamines, and glutamine) from HIV– NCs to HIV+ NCs and then HIV+ NCDs, reflecting a trend of increased oxidative stress. GPL metabolism emerges as the common metabolic disturbance linking HIV to NCDs, followed by glutamine and glutamate metabolism. Together, our data point to the aforementioned metabolisms and related metabolites as potential key targets in studying pathophysiology of NCDs in HIV infection and developing therapeutic interventions. China National Science and Technology Major Projects on Infectious Diseases, National Natural Science Foundation of China, Yi-wu Institute of Fudan University, and Shanghai Municipal Health and Family Planning Commission.
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影响因子：
19
作者：
Papsdorf K;Brunet A
通讯作者：
Brunet A
影响因子：
15.8
作者：
Licher, Silvan;Heshmatollah, Alis;Ikram, M. Arfan
通讯作者：
Ikram, M. Arfan
影响因子：
--
作者：
Gabuzda, Dana;Jamieson, Beth D;Hunt, Peter W
通讯作者：
Hunt, Peter W
影响因子：
13.5
作者：
Gaggini, Melania;Carli, Fabrizia;Gastaldelli, Amalia
通讯作者：
Gastaldelli, Amalia
影响因子：
4.6
作者：
Bowman, Emily;Funderburg, Nicholas T.
通讯作者：
Funderburg, Nicholas T.