title: Metabolite Modulation in Human Plasma in the Early Phase of Acclimatization to Hypobaric Hypoxia.
abstract: The exposure of healthy subjects to high altitude represents a model to explore the pathophysiology of diseases related to tissue hypoxia. We explored a plasma metabolomics approach to detect alterations induced by the exposure of subjects to high altitude. Plasma samples were collected from 60 subjects both on plain and at high altitude (5300 m). Metabolite profiling was performed by gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) in conjunction with univariate and multivariate statistical analyses. ELISA assays were further employed to measure the levels of several relevant enzymes together with perturbed metabolic pathways. The results showed that hypobaric hypoxia caused significant and comprehensive metabolic changes, as represented by significant changes of 44 metabolites and 4 relevant enzymes. Using MetaboAnalyst 3.0, it was found that several key metabolic pathways were acutely perturbed. In addition, 5 differentially expressed metabolites in pre-exposure samples from the acute mountain sickness-susceptible (AMS-S) group compared with those from the AMS-resistant (AMS-R) group are identified, which warrant further validation as potential predictive biomarkers for AMS-S individuals. These results provide new insights for further understanding the pathophysiological mechanism of early acclimatization to hypobaric hypoxia and other diseases correlated to tissue hypoxia.
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing 400038, China.|The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing 400038, China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Liao
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing 400038, China.|The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing 400038, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology and High Altitude Physiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing 400038, China.|The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing 400038, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: 18th Hospital, People's Liberation Army, Yecheng, Xinjiang, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Cui
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing 400038, China.|The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing 400038, China.
authors.forename: Yi-Xing
authors.initials: YX
authors.lastname: Gao
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing 400038, China.|The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing 400038, China.
authors.forename: Fu-Yu
authors.initials: FY
authors.lastname: Liu
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing 400038, China.|The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing 400038, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing 400038, China.|The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing 400038, China.
authors.forename: Bing-Da
authors.initials: BD
authors.lastname: Sun
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing 400038, China.|The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing 400038, China.
authors.forename: Er-Long
authors.initials: EL
authors.lastname: Zhang
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing 400038, China.|The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing 400038, China.
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Yuan
authors.affiliation: Department of High Altitude Military Hygiene, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing 400038, China.|The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing 400038, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing 400038, China.|The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing 400038, China.
authors.forename: Yu-Qi
authors.initials: YQ
authors.lastname: Gao
mesh_terms: D000208:Acute Disease; D000222:Adaptation, Physiological; D000532:Altitude Sickness / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D004198:Disease Susceptibility; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis*; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D011379:Prognosis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001798:Blood Proteins