1
|
Yoshida T, Kitada K, Nakai K, Uemura R, Kurihara Y, Tahara M, Hamuro A, Nakano A, Misugi T, Tachibana D. Elevated 12,13-diHOME level in maternal and umbilical cord blood complicated with preeclampsia. Front Endocrinol (Lausanne) 2024; 15:1445475. [PMID: 39439557 PMCID: PMC11493611 DOI: 10.3389/fendo.2024.1445475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 06/07/2024] [Accepted: 09/24/2024] [Indexed: 10/25/2024] Open
Abstract
Background Preeclampsia (PE) is a condition in pregnancy characterized by hypertension and proteinuria, thus leading to severe complications for both mother and fetus, including fetal growth restriction (FGR). However, there are still unclear aspects regarding the pathogenesis, prevention, and treatments. This study aimed to elucidate the characteristics of lipid metabolism in maternal and umbilical cord plasma complicated with PE using liquid chromatography-mass spectrometry (LC-MS). Method The study included singleton pregnant women at Osaka Metropolitan University Hospital from March 2023 to February 2024. PE was diagnosed based on new-onset hypertension after 20 weeks of gestation and other symptoms such as proteinuria and organ dysfunction. FGR was defined by ultrasound measurements below -1.5 standard deviation (SD). Plasma samples were collected from maternal and umbilical cord blood within 24 hours before delivery. Lipid metabolites were comprehensively analyzed using LC-MS, and the lipokine 12,13-diHOME, identified as elevated in the comprehensive analysis, was quantified. Immunohistochemistry was conducted on placental samples to assess soluble epoxide hydrolase (sEH) expression. Results The study involved 31 participants, with 20 in the control group and 11 in the PE group. A comprehensive analysis of maternal plasma samples identified a significant increase in 12,13-diHOME levels in the PE group compared to the control group. Quantification of 12,13-diHOME showed a significant increase in maternal plasma, umbilical venous plasma, and umbilical arterial plasma in the PE group compared to the control group (p = 0.007, p = 0.008, p = 0.005). PE with FGR showed significantly higher 12,13-diHOME concentrations in the umbilical arterial/venous ratio compared to the PE without FGR group (p = 0.03). Negative correlations were observed between 12,13-diHOME levels and birth weight in the PE group. Immunohistochemistry did not show significant differences in the sEH expression between the groups. Conclusion This study demonstrated that 12,13-diHOME levels were significantly elevated in maternal and umbilical cord blood in PE patients, particularly in PE with FGR. Elevated 12,13-diHOME may reflect the progression of placental ischemia due to PE pathogenesis. This lipid metabolite could serve as a marker for the severity of preeclampsia, thus providing new insights into perinatal lipidomics and the potential role of 12,13-diHOME in PE.
Collapse
Affiliation(s)
- Tomohiro Yoshida
- Department of Obstetrics and Gynecology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Kohei Kitada
- Department of Obstetrics and Gynecology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Kensaku Nakai
- Department of Obstetrics and Gynecology, Izumiotsu Municipal Hospital, Osaka, Japan
| | - Ryo Uemura
- Department of Obstetrics and Gynecology, Osaka City General Hospital, Osaka, Japan
| | - Yasushi Kurihara
- Department of Obstetrics and Gynecology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Mie Tahara
- Department of Obstetrics and Gynecology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Akihiro Hamuro
- Department of Obstetrics and Gynecology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Akemi Nakano
- Department of Obstetrics and Gynecology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Takuya Misugi
- Department of Obstetrics and Gynecology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Daisuke Tachibana
- Department of Obstetrics and Gynecology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| |
Collapse
|
2
|
Zhao ML, Lu ZJ, Yang L, Ding S, Gao F, Liu YZ, Yang XL, Li X, He SY. The cardiovascular system at high altitude: A bibliometric and visualization analysis. World J Cardiol 2024; 16:199-214. [PMID: 38690218 PMCID: PMC11056872 DOI: 10.4330/wjc.v16.i4.199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 11/22/2023] [Revised: 02/14/2024] [Accepted: 04/01/2024] [Indexed: 04/23/2024] Open
Abstract
BACKGROUND When exposed to high-altitude environments, the cardiovascular system undergoes various changes, the performance and mechanisms of which remain controversial. AIM To summarize the latest research advancements and hot research points in the cardiovascular system at high altitude by conducting a bibliometric and visualization analysis. METHODS The literature was systematically retrieved and filtered using the Web of Science Core Collection of Science Citation Index Expanded. A visualization analysis of the identified publications was conducted employing CiteSpace and VOSviewer. RESULTS A total of 1674 publications were included in the study, with an observed annual increase in the number of publications spanning from 1990 to 2022. The United States of America emerged as the predominant contributor, while Universidad Peruana Cayetano Heredia stood out as the institution with the highest publication output. Notably, Jean-Paul Richalet demonstrated the highest productivity among researchers focusing on the cardiovascular system at high altitude. Furthermore, Peter Bärtsch emerged as the author with the highest number of cited articles. Keyword analysis identified hypoxia, exercise, acclimatization, acute and chronic mountain sickness, pulmonary hypertension, metabolism, and echocardiography as the primary research hot research points and emerging directions in the study of the cardiovascular system at high altitude. CONCLUSION Over the past 32 years, research on the cardiovascular system in high-altitude regions has been steadily increasing. Future research in this field may focus on areas such as hypoxia adaptation, metabolism, and cardiopulmonary exercise. Strengthening interdisciplinary and multi-team collaborations will facilitate further exploration of the pathophysiological mechanisms underlying cardiovascular changes in high-altitude environments and provide a theoretical basis for standardized disease diagnosis and treatment.
Collapse
Affiliation(s)
- Mao-Lin Zhao
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Zhong-Jie Lu
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Li Yang
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Sheng Ding
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Feng Gao
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Yuan-Zhang Liu
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Xue-Lin Yang
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Xia Li
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Si-Yi He
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China.
| |
Collapse
|
3
|
Jin X, Zhang Y, Wang D, Zhang X, Li Y, Wang D, Liang Y, Wang J, Zheng L, Song H, Zhu X, Liang J, Ma J, Gao J, Tong J, Shi L. Metabolite and protein shifts in mature erythrocyte under hypoxia. iScience 2024; 27:109315. [PMID: 38487547 PMCID: PMC10937114 DOI: 10.1016/j.isci.2024.109315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 03/17/2024] Open
Abstract
As the only cell type responsible for oxygen delivery, erythrocytes play a crucial role in supplying oxygen to hypoxic tissues, ensuring their normal functions. Hypoxia commonly occurs under physiological or pathological conditions, and understanding how erythrocytes adapt to hypoxia is fundamental for exploring the mechanisms of hypoxic diseases. Additionally, investigating acute and chronic mountain sickness caused by plateaus, which are naturally hypoxic environments, will aid in the study of hypoxic diseases. In recent years, increasingly developed proteomics and metabolomics technologies have become powerful tools for studying mature enucleated erythrocytes, which has significantly contributed to clarifying how hypoxia affects erythrocytes. The aim of this article is to summarize the composition of the cytoskeleton and cytoplasmic proteins of hypoxia-altered erythrocytes and explore the impact of hypoxia on their essential functions. Furthermore, we discuss the role of microRNAs in the adaptation of erythrocytes to hypoxia, providing new perspectives on hypoxia-related diseases.
Collapse
Affiliation(s)
- Xu Jin
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Yingnan Zhang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Ding Wang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Xiaoru Zhang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Yue Li
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Di Wang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Yipeng Liang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Jingwei Wang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Lingyue Zheng
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Haoze Song
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Xu Zhu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Jing Liang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Jinfa Ma
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Jie Gao
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Jingyuan Tong
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Lihong Shi
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
- CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin 300020, China
| |
Collapse
|
4
|
Verma K, Amitabh, Prasad DN, Reddy MPK, Kohli E. Kynurenines Dynamics in the Periphery and Central Nervous System Steers Behavioral Deficits in Rats under Hypobaric Hypoxia. ACS Chem Neurosci 2024; 15:1084-1095. [PMID: 38462729 DOI: 10.1021/acschemneuro.3c00632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 03/12/2024] Open
Abstract
People travel to high-altitude regions as tourists, workers, and military personnel on duty. Despite the consistent 21% oxygen content in the atmosphere, ascending to higher altitudes results in a decrease in the partial pressure of oxygen, inducing a state known as hypobaric hypoxia (HH). HH is an environmental stress that is responsible for neuroinflammation and behavioral deficits (anxiety, depression, mood disturbance, etc.), but little is known about its metabolic pathways. The kynurenine pathway (KP) is a promising candidate to uncover the mysteries of HH stress, as it is an important regulator of the immune system and is associated with behavioral deficits. To investigate the role of KP under HH, the levels of KP metabolites in the serum, cerebrospinal fluid (CSF), and brain tissue (prefrontal cortex-PFC, neocortex, and hippocampus) of male Sprague-Dawley rats exposed to HH at 7620 m for 1, 3, and 7 days were estimated utilizing high-performance liquid chromatography (HPLC). The behavioral analogs for anxiety-like and depression-like behavior were assessed using the open field test and forced swim test, respectively. Upon HH exposure, crosstalk between the periphery and central nervous system and KP metabolite region-dependent differential expression in the brain were observed. KP metabolites showed a positive correlation with behavioral parameters. The results of our study are indicative that KP can be proposed as the etiology of behavioral deficits, and KP metabolite levels in serum or CSF can be used as plausible markers for anxiety-like and depression-like behaviors under HH stress with a scope of targeted therapeutic interventions.
Collapse
Affiliation(s)
- Kalyani Verma
- Department of Neurobiology, Defence Institute of Physiology and Allied Sciences, DRDO, Timarpur,Delhi 110054, India
| | - Amitabh
- Department of Neurobiology, Defence Institute of Physiology and Allied Sciences, DRDO, Timarpur,Delhi 110054, India
| | - Dipti N Prasad
- Department of Neurobiology, Defence Institute of Physiology and Allied Sciences, DRDO, Timarpur,Delhi 110054, India
| | - M Prasanna Kumar Reddy
- Department of Applied Physiology, Defence Institute of Physiology and Allied Sciences, DRDO, Timarpur, Delhi 110054, India
| | - Ekta Kohli
- Department of Neurobiology, Defence Institute of Physiology and Allied Sciences, DRDO, Timarpur,Delhi 110054, India
| |
Collapse
|
5
|
Chen CJ, Lee DY, Yu J, Lin YN, Lin TM. Recent advances in LC-MS-based metabolomics for clinical biomarker discovery. MASS SPECTROMETRY REVIEWS 2023; 42:2349-2378. [PMID: 35645144 DOI: 10.1002/mas.21785] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Academic Contribution Register] [Received: 09/03/2021] [Revised: 10/14/2021] [Accepted: 11/18/2021] [Indexed: 06/15/2023]
Abstract
The employment of liquid chromatography-mass spectrometry (LC-MS) untargeted and targeted metabolomics has led to the discovery of novel biomarkers and improved the understanding of various disease mechanisms. Numerous strategies have been reported to expand the metabolite coverage in LC-MS-untargeted and targeted metabolomics. To improve the sensitivity of low-abundance or poor-ionized metabolites for reducing the amount of clinical sample, chemical derivatization methods are used to target different functional groups. Proper sample preparation is beneficial for reducing the matrix effect, maintaining the stability of the LC-MS system, and increasing the metabolite coverage. Machine learning has recently been integrated into the workflow of LC-MS metabolomics to accelerate metabolite identification and data-processing automation, and increase the accuracy of disease classification and clinical outcome prediction. Due to the rapidly growing utility of LC-MS metabolomics in discovering disease markers, this review will address the recent advances in the field and offer perspectives on various strategies for expanding metabolite coverage, chemical derivatization, sample preparation, clinical disease markers, and machining learning for disease modeling.
Collapse
Affiliation(s)
- Chao-Jung Chen
- Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
- Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Der-Yen Lee
- Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Jiaxin Yu
- AI Innovation Center, China Medical University Hospital, Taichung, Taiwan
| | - Yu-Ning Lin
- Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Tsung-Min Lin
- Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| |
Collapse
|
6
|
Kim K, Choi J, Lee O, Lim J, Kim J. The Effects of Body Composition, Physical Fitness on Time of Useful Consciousness in Hypobaric Hypoxia. Mil Med 2023; 188:e2082-e2088. [PMID: 36583703 DOI: 10.1093/milmed/usac412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 09/20/2022] [Revised: 11/18/2022] [Accepted: 12/13/2022] [Indexed: 12/31/2022] Open
Abstract
INTRODUCTION Several previous studies have reported that hypoxia accidents of fighter pilots are rarer than gravity-induced loss of consciousness and spatial disorientation; however, the risk is greater. Therefore, this study aimed to investigate the relationship between physical fitness and body composition on time of useful consciousness (TUC) in hypobaric hypoxia. MATERIALS AND METHODS Body composition and physical fitness testing on human participants were performed; subsequently, they were exposed to hypobaric hypoxia at a simulated altitude of 25,000 ft. Cognitive testing of the participants was accomplished by having them perform arithmetic task tables until they stopped writing for a period exceeding 5 seconds, at which point, they were placed on 100% oxygen. TUC was measured from the time the participants removed their oxygen masks to the time when the oxygen masks were placed back on them. Pearson's correlation was used to determine the relationship between TUC and other variables, and multiple regression was performed to determine the independent variables that best explain the TUC. RESULTS TUC was positively correlated with the maximum oxygen uptake, stroke volume, arteriovenous oxygen difference, and endurance (sit-up and push-up). The maximum heart rate on the ground, high altitude, body fat mass, and percent body fat were negatively correlated with TUC. A regression analysis showed that 84.5% of the TUC can be explained by body composition and physical fitness. CONCLUSIONS Our results revealed that increased cardiorespiratory fitness and decreased body fat mass could significantly impact the TUC. Therefore, for Air Force pilots who are frequently at high altitudes and at risk for exposure to hypoxia, aerobic exercise is significant to hypoxia tolerance.
Collapse
Affiliation(s)
- Keunsoo Kim
- Department of Physical Education, Korea Air Force Academy, Cheongju-si, Chungcheongbuk-do 28187, Korea
| | - Jean Choi
- Department of Physical Education, Korea Air Force Academy, Cheongju-si, Chungcheongbuk-do 28187, Korea
| | - On Lee
- Korea Institute of Sports Science, Nowon-gu, Seoul 01794, Korea
| | - Jungjun Lim
- Department of Physical Education, College of Education, Seoul National University, Gwanak-gu, Seoul 08826, Korea
| | - Jungwoon Kim
- Department of Physical Education, Korea Air Force Academy, Cheongju-si, Chungcheongbuk-do 28187, Korea
| |
Collapse
|
7
|
Gao J, Zhao M, Cheng X, Yue X, Hao F, Wang H, Duan L, Han C, Zhu L. Metabolomic analysis of human plasma sample after exposed to high altitude and return to sea level. PLoS One 2023; 18:e0282301. [PMID: 36989280 PMCID: PMC10058093 DOI: 10.1371/journal.pone.0282301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 10/21/2022] [Accepted: 02/12/2023] [Indexed: 03/30/2023] Open
Abstract
When ascending to high altitude, it is a rigorous challenge to people who living in the low altitude area to acclimatize to hypoxic environment. Hypoxia exposure can cause dramatic disturbances of metabolism. This longitudinal cohort study was conducted to delineate the plasma metabolomics profile following exposure to altitude environments and explore potential metabolic changes after return to low altitude area. 25 healthy volunteers living in the low altitude area (Nor; 40m) were transported to high altitude (HA; 3,650m) for a 7-day sojourn before transported back to the low altitude area (HAP; 40m). Plasma samples were collected on the day before ascending to HA, the third day on HA(day 3) and the fourteenth day after returning to low altitude(14 day) and analyzed using UHPLC-MS/MS tools and then the data were subjected to multivariate statistical analyses. There were 737 metabolites were obtained in plasma samples with 133 significantly changed metabolites. We screened 13 differential metabolites that were significantly changed under hypoxia exposure; enriched metabolic pathways under hypoxia exposure including tryptophan metabolism, purine metabolism, regulation of lipolysis in adipocytes; We verified and relatively quantified eight targeted candidate metabolites including adenosine, guanosine, inosine, xanthurenic acid, 5-oxo-ETE, raffinose, indole-3-acetic acid and biotin for the Nor and HA group. Most of the metabolites recovered when returning to the low altitude area, however, there were still 6 metabolites that were affected by hypoxia exposure. It is apparent that high-altitude exposure alters the metabolic characteristics and two weeks after returning to the low altitude area a small portion of metabolites was still affected by high-altitude exposure, which indicated that high-altitude exposure had a long-term impact on metabolism. This present longitudinal cohort study demonstrated that metabolomics can be a useful tool to monitor metabolic changes exposed to high altitude, providing new insight in the attendant health problem that occur in response to high altitude.
Collapse
Affiliation(s)
- Jiayue Gao
- Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Ming Zhao
- Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Xiang Cheng
- Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Xiangpei Yue
- Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Fangbin Hao
- The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Hui Wang
- The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Lian Duan
- The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Cong Han
- The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Lingling Zhu
- Beijing Institute of Basic Medical Sciences, Beijing, China
- Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China
| |
Collapse
|
8
|
Dünnwald T, Paglia G, Weiss G, Denti V, Faulhaber M, Schobersberger W, Wackerhage H. High Intensity Concentric-Eccentric Exercise Under Hypoxia Changes the Blood Metabolome of Trained Athletes. Front Physiol 2022; 13:904618. [PMID: 35812339 PMCID: PMC9260056 DOI: 10.3389/fphys.2022.904618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 03/25/2022] [Accepted: 06/01/2022] [Indexed: 11/19/2022] Open
Abstract
The aim of this study was to determine alterations of the metabolome in blood plasma in response to concentric-eccentric leg exercise performed at a simulated altitude of 3,500 m. To do so, we recruited 11 well-trained subjects and performed an untargeted metabolomics analysis of plasma samples obtained before, 20 min after as well as on day 8 after five sets of maximal, concentric-eccentric leg exercises that lasted 90 s each. We identified and annotated 115 metabolites through untargeted liquid chromatography-mass spectrometry metabolomics and used them to further calculate 20 sum/ratio of metabolites. A principal component analysis (PCA) revealed differences in-between the overall metabolome at rest and immediately after exercise. Interestingly, some systematic changes of relative metabolite concentrations still persisted on day 8 after exercise. The first two components of the PCA explained 34% of the relative concentrations of all identified metabolites analyzed together. A volcano plot indicates that 35 metabolites and two metabolite ratios were significantly changed directly after exercise, such as metabolites related to carbohydrate and TCA metabolism. Moreover, we observed alterations in the relative concentrations of amino acids (e.g., decreases of valine, leucine and increases in alanine) and purines (e.g., increases in hypoxanthine, xanthine and uric acid). In summary, high intensity concentric-eccentric exercise performed at simulated altitude systematically changed the blood metabolome in trained athletes directly after exercise and some relative metabolite concentrations were still changed on day 8. The importance of that persisting metabolic alterations on exercise performance should be studied further.
Collapse
Affiliation(s)
- Tobias Dünnwald
- Institute for Sports Medicine, Alpine Medicine and Health Tourism (ISAG), UMIT TIROL, Private University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria
- *Correspondence: Tobias Dünnwald,
| | - Giuseppe Paglia
- School of Medicine and Surgery, University of Milano-Bicocca, Vedano al Lambro (MB), Italy
| | - Günter Weiss
- Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria
| | - Vanna Denti
- School of Medicine and Surgery, University of Milano-Bicocca, Vedano al Lambro (MB), Italy
| | - Martin Faulhaber
- Department of Sport Science, University of Innsbruck, Innsbruck, Austria
| | - Wolfgang Schobersberger
- Institute for Sports Medicine, Alpine Medicine and Health Tourism (ISAG), UMIT TIROL, Private University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria
- Tirol-Kliniken GmbH, Innsbruck, Austria
| | - Henning Wackerhage
- Department of Sport and Health Sciences, Technische Universität München, Munich, Germany
| |
Collapse
|
9
|
Gandhi S, Chinnadurai V, Bhadra K, Gupta I, Kanwar RS. Urinary metabolic modulation in human participants residing in Siachen: a 1H NMR metabolomics approach. Sci Rep 2022; 12:9070. [PMID: 35641596 PMCID: PMC9156790 DOI: 10.1038/s41598-022-13031-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 02/18/2022] [Accepted: 05/19/2022] [Indexed: 12/15/2022] Open
Abstract
The main physiological challenge in high altitude environment is hypoxia which affects the aerobic metabolism reducing the energy supply. These changes may further progress toward extreme environment-related diseases. These are further reflected in changes in small molecular weight metabolites and metabolic pathways. In the present study, metabolic changes due to chronic environmental hypoxia were assessed using 1H NMR metabolomics by analysing the urinary metabolic profile of 70 people at sea level and 40 people at Siachen camp (3700 m) for 1 year. Multivariate statistical analysis was carried out, and PLSDA detected 15 metabolites based on VIP score > 1. ROC analysis detected cis-aconitate, Nicotinamide Mononucleotide, Tyrosine, Choline and Creatinine metabolites with a high range of sensitivity and specificity. Pathway analysis revealed 16 pathways impact > 0.05, and phenylalanine tyrosine and tryptophan biosynthesis was the most prominent altered pathway indicating metabolic remodelling to meet the energy requirements. TCA cycle, Glycine serine and Threonine metabolism, Glutathione metabolism and Cysteine alterations were other metabolic pathways affected during long-term high-altitude hypoxia exposure. Present findings will help unlock a new dimension for the potential application of NMR metabolomics to address extreme environment-related health problems, early detection and developing strategies to combat high altitude hypoxia.
Collapse
Affiliation(s)
- Sonia Gandhi
- Metabolomics Research Facility, Institute of Nuclear Medicine and Allied Sciences (INMAS), Lucknow Road, Timarpur, Delhi, 110054, India.
| | - Vijayakumar Chinnadurai
- Cognitive Control and Machine Learning Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, 110054, India
| | - Kuntal Bhadra
- Department of Endocrinology and Thyroid Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, 110054, India
| | - Isha Gupta
- Metabolomics Research Facility, Institute of Nuclear Medicine and Allied Sciences (INMAS), Lucknow Road, Timarpur, Delhi, 110054, India
| | - Ratnesh Singh Kanwar
- Department of Endocrinology and Thyroid Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, 110054, India
| |
Collapse
|
10
|
Gut Microbiome-Targeted Modulations Regulate Metabolic Profiles and Alleviate Altitude-Related Cardiac Hypertrophy in Rats. Microbiol Spectr 2022; 10:e0105321. [PMID: 35138162 PMCID: PMC8826942 DOI: 10.1128/spectrum.01053-21] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 01/01/2023] Open
Abstract
It is well known that humans physiologically or pathologically respond to high altitude, with these responses accompanied by alterations in the gut microbiome. To investigate whether gut microbiota modulation can alleviate high-altitude-related diseases, we administered probiotics, prebiotics, and synbiotics in rat model with altitude-related cardiac impairment after hypobaric hypoxia challenge and observed that all three treatments alleviated cardiac hypertrophy as measured by heart weight-to-body weight ratio and gene expression levels of biomarkers in heart tissue. The disruption of gut microbiota induced by hypobaric hypoxia was also ameliorated, especially for microbes of Ruminococcaceae and Lachnospiraceae families. Metabolome revealed that hypobaric hypoxia significantly altered the plasma short-chain fatty acids (SCFAs), bile acids (BAs), amino acids, neurotransmitters, and free fatty acids, but not the overall fecal SCFAs and BAs. The treatments were able to restore homeostasis of plasma amino acids and neurotransmitters to a certain degree, but not for the other measured metabolites. This study paves the way to further investigate the underlying mechanisms of gut microbiome in high-altitude related diseases and opens opportunity to target gut microbiome for therapeutic purpose. IMPORTANCE Evidence suggests that gut microbiome changes upon hypobaric hypoxia exposure; however, it remains elusive whether this microbiome change is a merely derivational reflection of host physiological alteration, or it synergizes to exacerbate high-altitude diseases. We intervened gut microbiome in the rat model of prolonged hypobaric hypoxia challenge and found that the intervention could alleviate the symptoms of pathological cardiac hypertrophy, gut microbial dysbiosis, and metabolic disruptions of certain metabolites in gut and plasma induced by hypobaric hypoxia. Our study suggests that gut microbiome may be a causative factor for high-altitude-related pathogenesis and a target for therapeutic intervention.
Collapse
|
11
|
Cas MD, Morano C, Ottolenghi S, Dicasillati R, Roda G, Samaja M, Paroni R. Inside the Alterations of Circulating Metabolome in Antarctica: The Adaptation to Chronic Hypoxia. Front Physiol 2022; 13:819345. [PMID: 35145434 PMCID: PMC8821919 DOI: 10.3389/fphys.2022.819345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 11/21/2021] [Accepted: 01/04/2022] [Indexed: 11/21/2022] Open
Abstract
Although the human body may dynamically adapt to mild and brief oxygen shortages, there is a growing interest in understanding how the metabolic pathways are modified during sustained exposure to chronic hypoxia. Located at an equivalent altitude of approximately 3,800 m asl, the Concordia Station in Antarctica represents an opportunity to study the course of human adaption to mild hypoxia with reduced impact of potentially disturbing variables else than oxygen deprivation. We recruited seven healthy subjects who spent 10 months in the Concordia Station, and collected plasma samples at sea level before departure, and 90 days, 6 months, and 10 months during hypoxia. Samples were analyzed by untargeted liquid chromatography high resolution mass spectrometry to unravel how the non-polar and polar metabolomes are affected. Statistical analyses were performed by clustering the subjects into four groups according to the duration of hypoxia exposure. The non-polar metabolome revealed a modest decrease in the concentration of all the major lipid classes. By contrast, the polar metabolome showed marked alterations in several metabolic pathways, especially those related to amino acids metabolism, with a particular concern of arginine, glutamine, phenylalanine, tryptophan, and tyrosine. Remarkably, all the changes were evident since the first time point and remained unaffected by hypoxia duration (with the exception of a slight return of the non-polar metabolome after 6 months), highlighting a relative inability of the body to compensate them. Finally, we identified a few metabolic pathways that emerged as the main targets of chronic hypoxia.
Collapse
Affiliation(s)
- Michele Dei Cas
- Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Camillo Morano
- Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Sara Ottolenghi
- Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
- Department of Medicine and Surgery, Università degli Studi di Milano-Bicocca, Milan, Italy
| | - Roberto Dicasillati
- Department of General Surgery, ASST Santi Paolo e Carlo, San Paolo Hospital, Milan, Italy
| | - Gabriella Roda
- Department of Pharmaceutical Sciences, Università degli Studi di Milano, Milan, Italy
| | - Michele Samaja
- Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
- MAGI Group, Brescia, Italy
- *Correspondence: Michele Samaja,
| | - Rita Paroni
- Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| |
Collapse
|
12
|
Huang M, Zhang X, Yan W, Liu J, Wang H. Metabolomics reveals potential plateau adaptability by regulating
inflammatory response and oxidative stress-related metabolism and energy
metabolism pathways in yak. JOURNAL OF ANIMAL SCIENCE AND TECHNOLOGY 2021; 64:97-109. [PMID: 35174345 PMCID: PMC8819316 DOI: 10.5187/jast.2021.e129] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Academic Contribution Register] [Received: 10/04/2021] [Revised: 11/14/2021] [Accepted: 11/30/2021] [Indexed: 11/23/2022]
Abstract
Species are facing strong selection pressures to adapt to inhospitable
high-altitude environments. Yaks are a valuable species and an iconic symbol of
the Qinghai-Tibet Plateau. Extensive studies of high-altitude adaptation have
been conducted, but few have focused on metabolism. In the present study, we
determined the differences in the serum metabolomics between yaks and the
closely related species of low-altitude yellow cattle and dairy cows. We
generated high-quality metabolite profiling data for 36 samples derived from the
three species, and a clear separation trend was obtained between yaks and the
other animals from principal component analysis. In addition, we identified a
total of 63 differentially expressed metabolites among the three species.
Functional analysis revealed that differentially expressed metabolites were
related to the innate immune activation, oxidative stress-related metabolism,
and energy metabolism in yaks, which indicates the important roles of
metabolites in high-altitude adaptation in yaks. The results provide new
insights into the mechanism of adaptation or acclimatization to high-altitude
environments in yaks and hypoxia-related diseases in humans.
Collapse
Affiliation(s)
- Meizhou Huang
- Department of Toxicology, School of Public
Health, Lanzhou University, Gansu 730000, China
- Academician (Expert) Workstation of
Sichuan Province, The Affiliated Hospital of Southwest Medical
University, Sichuan 646000, China
| | - Xin Zhang
- Department of Toxicology, School of Public
Health, Lanzhou University, Gansu 730000, China
| | - Wenjun Yan
- Agricultural and Rural Integrated Service
Center of Dachaigou Town, Tianzhu Tibetan Autonomous County,
Gansu 733202, China
| | - Jingjing Liu
- Department of Toxicology, School of Public
Health, Lanzhou University, Gansu 730000, China
| | - Hui Wang
- Department of Toxicology, School of Public
Health, Lanzhou University, Gansu 730000, China
- Corresponding author: Hui Wang, Department of
Toxicology, School of Public Health, Lanzhou University, Gansu 730000, China.
Tel: +86-13919330832, E-mail:
| |
Collapse
|
13
|
Fan L, Wang F, Yao Q, Wu H, Wen F, Wang J, Li H, Zheng N. Lactoferrin could alleviate liver injury caused by Maillard reaction products with furan ring through regulating necroptosis pathway. Food Sci Nutr 2021; 9:3449-3459. [PMID: 34262705 PMCID: PMC8269604 DOI: 10.1002/fsn3.2254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 10/30/2020] [Revised: 03/09/2021] [Accepted: 03/11/2021] [Indexed: 11/07/2022] Open
Abstract
As classical MRPs, the toxic effects of furosine, pyralline, and 5-hydroxymethylfurfural (5-HMF) in liver tissue are evaluated and the related mechanism is investigated here, and the protective effects of lactoferrin on liver injury caused by Maillard reaction products (MRPs) with furan ring are proved in vitro and in vivo. First, we detect the concentrations of furosine, pyralline, and 5-HMF in several foods using ultrahigh-performance liquid chromatography (UHPLC). Then, the effects of the three MRPs on liver cells (HL-7702) viability, as well as liver tissue, are performed and evaluated. Furthermore, the regulations of three MRPs on necroptosis-related pathway in liver cells are investigated. Additionally, the effects of lactoferrin in alleviating liver injury, as well as regulating necroptosis pathway, were evaluated. Results elucidate that lactoferrin protects liver injury caused by MRPs with furan ring structure through activating RIPK1/RIPK3/p-MLKL necroptosis pathway and downstream inflammatory reaction.
Collapse
Affiliation(s)
- Linlin Fan
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Fengen Wang
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Qianqian Yao
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Haoming Wu
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Fang Wen
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Jiaqi Wang
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Huiying Li
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Nan Zheng
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| |
Collapse
|
14
|
Margolis LM, Karl JP, Wilson MA, Coleman JL, Ferrando AA, Young AJ, Pasiakos SM. Metabolomic profiles are reflective of hypoxia-induced insulin resistance during exercise in healthy young adult males. Am J Physiol Regul Integr Comp Physiol 2021; 321:R1-R11. [PMID: 33949213 PMCID: PMC8321788 DOI: 10.1152/ajpregu.00076.2021] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 01/01/2023]
Abstract
Hypoxia-induced insulin resistance appears to suppress exogenous glucose oxidation during metabolically matched aerobic exercise during acute (<8 h) high-altitude (HA) exposure. However, a better understanding of this metabolic dysregulation is needed to identify interventions to mitigate these effects. The objective of this study was to determine if differences in metabolomic profiles during exercise at sea level (SL) and HA are reflective of hypoxia-induced insulin resistance. Native lowlanders (n = 8 males) consumed 145 g (1.8 g/min) of glucose while performing 80-min of metabolically matched treadmill exercise at SL (757 mmHg) and HA (460 mmHg) after 5-h exposure. Exogenous glucose oxidation and glucose turnover were determined using indirect calorimetry and dual tracer technique ([13C]glucose and [6,6-2H2]glucose). Metabolite profiles were analyzed in serum as change (Δ), calculated by subtracting postprandial/exercised state SL (ΔSL) and HA (ΔHA) from fasted, rested conditions at SL. Compared with SL, exogenous glucose oxidation, glucose rate of disappearance, and glucose metabolic clearance rate (MCR) were lower (P < 0.05) during exercise at HA. One hundred and eighteen metabolites differed between ΔSL and ΔHA (P < 0.05, Q < 0.10). Differences in metabolites indicated increased glycolysis, tricarboxylic acid cycle, amino acid catabolism, oxidative stress, and fatty acid storage, and decreased fatty acid mobilization for ΔHA. Branched-chain amino acids and oxidative stress metabolites, Δ3-methyl-2-oxobutyrate (r = -0.738) and Δγ-glutamylalanine (r = -0.810), were inversely associated (P < 0.05) with Δexogenous glucose oxidation. Δ3-Hydroxyisobutyrate (r = -0.762) and Δ2-hydroxybutyrate/2-hydroxyisobutyrate (r = -0.738) were inversely associated (P < 0.05) with glucose MCR. Coupling global metabolomics and glucose kinetic data suggest that the underlying cause for diminished exogenous glucose oxidative capacity during aerobic exercise is acute hypoxia-mediated peripheral insulin resistance.
Collapse
Affiliation(s)
- Lee M Margolis
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts
| | - J Philip Karl
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts
| | - Marques A Wilson
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts
| | - Julie L Coleman
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts.,Oak Ridge Institute of Science and Education, Oak Ridge, Tennessee
| | - Arny A Ferrando
- Department of Geriatrics, Center for Translational Research in Aging and Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Andrew J Young
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts.,Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland
| | - Stefan M Pasiakos
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts
| |
Collapse
|
15
|
Xu G, Shi YK, Sun BD, Liu L, E GJ, He S, Zhang JY, Liu B, Hu Q, Chen J, Gao YQ, Zhang EL. DL-3-n-butylphthalide improved physical and learning and memory performance of rodents exposed to acute and chronic hypobaric hypoxia. Mil Med Res 2021; 8:23. [PMID: 33766114 PMCID: PMC7993509 DOI: 10.1186/s40779-021-00314-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 07/01/2020] [Accepted: 03/08/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Studies have revealed the protective effect of DL-3-n-butylphthalide (NBP) against diseases associated with ischemic hypoxia. However, the role of NBP in animals with hypobaric hypoxia has not been elucidated. This study investigated the effects of NBP on rodents with acute and chronic hypobaric hypoxia. METHODS Sprague-Dwaley rats and Kunming mice administered with NBP (0, 60, 120, and 240 mg/kg for rats and 0, 90, 180, and 360 mg/kg for mice) were placed in a hypobaric hypoxia chamber at 10,000 m and the survival percentages at 30 min were determined. Then, the time and distance to exhaustion of drug-treated rodents were evaluated during treadmill running and motor-driven wheel-track treadmill experiments, conducted at 5800 m for 3 days or 20 days, to evaluate changes in physical functions. The frequency of active escapes and duration of active escapes were also determined for rats in a shuttle-box experiment, conducted at 5800 m for 6 days or 27 days, to evaluate changes in learning and memory function. ATP levels were measured in the gastrocnemius muscle and malonaldehyde (MDA), superoxide dismutase (SOD), hydrogen peroxide (H2O2), glutathione peroxidase (GSH-Px), and lactate were detected in sera of rats, and routine blood tests were also performed. RESULTS Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance ability. The time and distance to exhaustion for mice (NBP, 90 mg/kg) and time to exhaustion for rats (NBP, 120 and 240 mg/kg) significantly increased under conditions of acute hypoxia compared with control group. NBP treatment also significantly increased the time to exhaustion for rats when exposed to chronic hypoxia. Moreover, 240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute hypoxia. Furthermore, the levels of MDA and H2O2 decreased but those of SOD and GSH-Px in the sera of rats increased under conditions of acute and chronic hypoxia. Additionally, ATP levels in the gastrocnemius muscle significantly increased, while lactate levels in sera significantly decreased. CONCLUSION NBP improved physical and learning and memory functions in rodents exposed to acute or chronic hypobaric hypoxia by increasing their anti-oxidative capacity and energy supply.
Collapse
Affiliation(s)
- Gang Xu
- Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Yi-Kun Shi
- Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Bin-Da Sun
- Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Lu Liu
- Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Guo-Ji E
- Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Shu He
- Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Jian-Yang Zhang
- Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Bao Liu
- Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Qiu Hu
- Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Jian Chen
- Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China.,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Yu-Qi Gao
- Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China. .,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China. .,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China.
| | - Er-Long Zhang
- Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China. .,Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China. .,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China.
| |
Collapse
|
16
|
Khanna K, Mishra KP, Chanda S, Ganju L, Singh SB, Kumar B. Effect of Synbiotics on Amelioration of Intestinal Inflammation Under Hypobaric Hypoxia. High Alt Med Biol 2020; 22:32-44. [PMID: 33185493 DOI: 10.1089/ham.2020.0062] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 01/21/2023] Open
Abstract
Khanna, Kunjan, Kamla Prasad Mishra, Sudipta Chanda, Lilly Ganju, Shashi Bala Singh, and Bhuvnesh Kumar. Effect of synbiotics on amelioration of intestinal inflammation under hypobaric hypoxia. High Alt Med Biol. 22:32-44, 2021. Aim: High-altitude exposure alters the gastrointestinal (GI) system, which may be a cause of hypobaric hypoxia (HH)-induced microbial dysbiosis. Therefore, we investigated the effect of a combination of beneficial bacteria and nondigestible fiber popularly known as "synbiotics" (Syn) to mitigate intestinal inflammation and microbial dysbiosis post-HH exposure. Methods: Syn, that is, a combination of probiotics and prebiotics, was given to male Sprague-Dawley rats 3 days prior and along with the HH exposure to assess its effect on mucosal barrier injury and inflammation. Changes in the gut microbiota and functional analysis were assessed using 16S rRNA and whole-genome sequencing (WGS) analysis. Results: Syn treatment significantly improved mucosal barrier injury in terms of decreased serum fluorescein isothiocyanate dextran from 96.1 ± 7.95 μg/ml in HH-alone group to 38.35 ± 4.55 μg/ml in HH + Syn group (p < 0.01) and decreased serum zonulin levels, that is, from 134.7 ± 19.05 ng/ml (HH alone) to 64.02 ± 7.33 ng/ml (HH + Syn) (p < 0.05), along with improvement in the intestinal villi under HH exposure. Levels of proinflammatory cytokines and chemokines significantly reduced upon Syn treatment, indicating attenuation of inflammation and immune cell migration. Syn treatment significantly reduced Th17 biased immune response preventing interleukin (IL)-17-induced inflammatory response with 8.1 ± 0.5 ng/mg protein in HH exposure group, while treatment with Syn in HH-exposed group reduced IL-17 levels to 2.01 ± 0.3 ng/mg protein (p < 0.001). Analysis of 16S rRNA showed significant (p < 0.05) alterations in Deferribacteres, Firmicutes, and Verrucomicrobia at the phylum levels, whereas Prevotella, Paenibacillus, Clostridium, Turicibacter, Bacillus, Anoxybacillus, Enterococcus, SMB53, Mucispirillum, Allobaculum, and Lactococcus were significantly altered (p < 0.05) in abundance at the genus level. WGS analysis revealed improvement in GI health by regulating functional pathways post-Syn treatment. Conclusion: Our findings indicate that Syn treatment improves intestinal barrier function and curtailed inflammation in the HH-exposed rat models, proving it to be a promising potential countermeasure for HH-induced gut problems.
Collapse
Affiliation(s)
- Kunjan Khanna
- Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences, Delhi, India
| | - Kamla Prasad Mishra
- Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences, Delhi, India
| | - Sudipta Chanda
- Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences, Delhi, India
| | - Lilly Ganju
- Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences, Delhi, India
| | - Shashi Bala Singh
- National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Bhuvnesh Kumar
- Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences, Delhi, India
| |
Collapse
|
17
|
Liao W, Liu J, Wang S, Xue Z, Zheng F, Feng F, Liu W. Metabolic profiling reveals that salidroside antagonizes hypoxic injury via modulating energy and lipid metabolism in cardiomyocytes. Biomed Pharmacother 2020; 122:109700. [DOI: 10.1016/j.biopha.2019.109700] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 07/22/2019] [Revised: 10/21/2019] [Accepted: 11/24/2019] [Indexed: 12/20/2022] Open
|
18
|
Abstract
Oxygen deficiency in the plateau environment weakens aerobic metabolism and reduces the energy supply, leading to high-altitude diseases including decreased circulatory function, decreased nutrient and energy supply to tissues and organs, and decreased waste discharge. The involvement of many metabolic pathways is reflected in dramatic changes in levels of endogenous small molecule metabolites. Metabolomics represents a promising technique for mechanistic studies and drug screening, and metabonomics, or quantitative metabolomics, has been increasingly applied to the study of hypoxic diseases and their pathogenesis, as well as to pharmacodynamics at high altitudes. In this article, we review the recent literature on the pathogenesis of altitude hypoxia and the clinical and preclinical metabonomics of drug interventions. Endogenous metabolites and metabolic pathways change significantly under high-altitude hypoxia. Some drug interventions have also been shown to regulate pathway metabolism, and the problems of applying metabonomics to hypoxic diseases at high altitude and the prospects for its future application are summarized.
Collapse
Affiliation(s)
- Yue Chang
- Department of Hepatopancreatobiliary and Splenic Medicine, Characteristic Medical Center of People's Armed Police Force, Tianjin, China.,Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis and Treatment, Tianjin, China
| | - Wen Zhang
- Department of Hepatopancreatobiliary and Splenic Medicine, Characteristic Medical Center of People's Armed Police Force, Tianjin, China.,Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis and Treatment, Tianjin, China
| | - Kai Chen
- Department of Hepatopancreatobiliary and Splenic Medicine, Characteristic Medical Center of People's Armed Police Force, Tianjin, China.,Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis and Treatment, Tianjin, China
| | - Zhenguo Wang
- Department of Hepatopancreatobiliary and Splenic Medicine, Characteristic Medical Center of People's Armed Police Force, Tianjin, China
| | - Shihai Xia
- Department of Hepatopancreatobiliary and Splenic Medicine, Characteristic Medical Center of People's Armed Police Force, Tianjin, China.,Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis and Treatment, Tianjin, China
| | - Hai Li
- Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis and Treatment, Tianjin, China.,Division of Gastroenterology and Hepatology, Tianjin Xiqing Hospital, Tianjin, China
| |
Collapse
|
19
|
Furosine, a Maillard Reaction Product, Triggers Necroptosis in Hepatocytes by Regulating the RIPK1/RIPK3/MLKL Pathway. Int J Mol Sci 2019; 20:ijms20102388. [PMID: 31091743 PMCID: PMC6566718 DOI: 10.3390/ijms20102388] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 04/26/2019] [Revised: 05/11/2019] [Accepted: 05/13/2019] [Indexed: 12/22/2022] Open
Abstract
As one of the typical Maillard reaction products, furosine has been widely reported in a variety of heat-processed food. Though furosine was shown to be toxic on organs, its toxicity mechanism is still unclear. The present study aimed to investigate the toxicity mechanism of furosine in liver tissue. An intragastric gavage mice model (42-day administration, 0.1/0.25/0.5 g/kg of furosine per day) and a mice primary hepatocyte model were employed to investigate the toxicity mechanism of furosine on mice liver tissue. A metabonomics analysis of mice liver, serum, and red blood cells (RBC) was performed. The special metabolic mediator of furosine, lysophosphatidylcholine 18:0 (LPC (18:0)) was identified. Then, the effect of the upstream gene phospholipase A2 gamma (PLA2-3) on LPC (18:0), as well as the effect of furosine (100 mg/L) on the receptor-interacting serine/threonine-protein kinase (RIPK)1/RIPK3/mixed lineage kinase domain-like protein (MLKL) pathway and inflammatory factors, was determined in liver tissue and primary hepatocytes. PLA2-3 was found to regulate the level of LPC (18:0) and activate the expression of RIPK1, RIPK3, P-MLKL, and of the inflammatory factors including tumor necrosis factor α (TNF-α) and interleukin (IL-1β), both in liver tissue and in primary hepatocytes. Upon treatment with furosine, the upstream sensor PLA2-3 activated the RIPK1/RIPK3/MLKL necroptosis pathway and caused inflammation by regulating the expression of LPC (18:0), which further caused liver damage.
Collapse
|
20
|
Distinct influence of COX-1 and COX-2 on neuroinflammatory response and associated cognitive deficits during high altitude hypoxia. Neuropharmacology 2019; 146:138-148. [DOI: 10.1016/j.neuropharm.2018.11.026] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 07/10/2018] [Revised: 10/26/2018] [Accepted: 11/16/2018] [Indexed: 02/08/2023]
|
21
|
Liao WT, Liu J, Zhou SM, Xu G, Gao YQ, Liu WY. UHPLC-QTOFMS-Based Metabolomic Analysis of the Hippocampus in Hypoxia Preconditioned Mouse. Front Physiol 2019; 9:1950. [PMID: 30687133 PMCID: PMC6335317 DOI: 10.3389/fphys.2018.01950] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 10/16/2017] [Accepted: 12/22/2018] [Indexed: 01/22/2023] Open
Abstract
Background: Hypoxia appears in a number of extreme environments, including high altitudes, the deep sea, and during aviation, and occurs in cancer, cardiovascular disease, respiratory failures and neurological disorders. Though it is well recognized that hypoxic preconditioning (HPC) exerts endogenous neuroprotective effect against severe hypoxia, the mediators and underlying molecular mechanism for the protective effect are still not fully understood. This study established a hippocampus metabolomics approach to explore the alterations associated with HPC. Methods: In this study, an animal model of HPC was established by exposing the adult BALB/c mice to acute repetitive hypoxia four times. Ultra-high liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) in combination with univariate and multivariate statistical analyses was employed to deciphering metabolic changes associated with HPC in hippocampus tissue. MetaboAnalyst 3.0 was used to construct HPC related metabolic pathways. Results: The significant metabolic differences in hippocampus between the HPC groups and control were observed, indicating that HPC mouse model was successfully established and HPC could caused significant metabolic changes. Several key metabolic pathways were found to be acutely perturbed, including phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine metabolism, phenylalanine metabolism, glutathione metabolism, alanine, aspartate and glutamate metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, citrate cycle, and glycerophospholipid metabolism. Conclusion: The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the neuroprotective mechanism of HPC.
Collapse
Affiliation(s)
- Wen-Ting Liao
- Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, China
| | - Jie Liu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Military Medical University, Chongqing, China.,The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Si-Min Zhou
- The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China.,Department of High Altitude Military Hygiene, College of High Altitude Military Medicine, Army Military Medical University, Chongqing, China
| | - Gang Xu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Military Medical University, Chongqing, China.,The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Yu-Qi Gao
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Military Medical University, Chongqing, China.,The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Wen-Yuan Liu
- Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, China
| |
Collapse
|
22
|
Lawler NG, Abbiss CR, Gummer JPA, Broadhurst DI, Govus AD, Fairchild TJ, Thompson KG, Garvican-Lewis LA, Gore CJ, Maker GL, Trengove RD, Peiffer JJ. Characterizing the plasma metabolome during 14 days of live-high, train-low simulated altitude: A metabolomic approach. Exp Physiol 2018; 104:81-92. [PMID: 30311980 DOI: 10.1113/ep087159] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 06/12/2018] [Accepted: 10/11/2018] [Indexed: 02/06/2023]
Abstract
NEW FINDINGS What is the central question of this study? Does 14 days of live-high, train-low simulated altitude alter an individual's metabolomic/metabolic profile? What is the main finding and its importance? This study demonstrated that ∼200 h of moderate simulated altitude exposure resulted in greater variance in measured metabolites between subject than within subject, which indicates individual variability during the adaptive phase to altitude exposure. In addition, metabolomics results indicate that altitude alters multiple metabolic pathways, and the time course of these pathways is different over 14 days of altitude exposure. These findings support previous literature and provide new information on the acute adaptation response to altitude. ABSTRACT The purpose of this study was to determine the influence of 14 days of normobaric hypoxic simulated altitude exposure at 3000 m on the human plasma metabolomic profile. For 14 days, 10 well-trained endurance runners (six men and four women; 29 ± 7 years of age) lived at 3000 m simulated altitude, accumulating 196.4 ± 25.6 h of hypoxic exposure, and trained at ∼600 m. Resting plasma samples were collected at baseline and on days 3 and 14 of altitude exposure and stored at -80°C. Plasma samples were analysed using liquid chromatography-high-resolution mass spectrometry to construct a metabolite profile of altitude exposure. Mass spectrometry of plasma identified 36 metabolites, of which eight were statistically significant (false discovery rate probability 0.1) from baseline to either day 3 or day 14. Specifically, changes in plasma metabolites relating to amino acid metabolism (tyrosine and proline), glycolysis (adenosine) and purine metabolism (adenosine) were observed during altitude exposure. Principal component canonical variate analysis showed significant discrimination between group means (P < 0.05), with canonical variate 1 describing a non-linear recovery trajectory from baseline to day 3 and then back to baseline by day 14. Conversely, canonical variate 2 described a weaker non-recovery trajectory and increase from baseline to day 3, with a further increase from day 3 to 14. The present study demonstrates that metabolomics can be a useful tool to monitor metabolic changes associated with altitude exposure. Furthermore, it is apparent that altitude exposure alters multiple metabolic pathways, and the time course of these changes is different over 14 days of altitude exposure.
Collapse
Affiliation(s)
- Nathan G Lawler
- School of Psychology and Exercise Science, Murdoch University, Murdoch, WA, Australia.,Separation Science and Metabolomics Laboratory, Murdoch University, Murdoch, WA, Australia.,Centre for Integrative Metabolomics and Computational Biology, School of Sciences, Edith Cowan University, Joondalup, WA, Australia
| | - Chris R Abbiss
- Centre for Exercise and Sport Science Research, School of Exercise and Health Science, Edith Cowan University, Joondalup, WA, Australia
| | - Joel P A Gummer
- Separation Science and Metabolomics Laboratory, Murdoch University, Murdoch, WA, Australia.,Metabolomics Australia, Murdoch University Node, Murdoch, WA, Australia
| | - David I Broadhurst
- Centre for Integrative Metabolomics and Computational Biology, School of Sciences, Edith Cowan University, Joondalup, WA, Australia
| | - Andrew D Govus
- Department of Rehabilitation, Nutrition and Sport, School of Allied Health, La Trobe University, Melbourne, Victoria, Australia
| | - Timothy J Fairchild
- School of Psychology and Exercise Science, Murdoch University, Murdoch, WA, Australia
| | - Kevin G Thompson
- Research Institute of Sport and Exercise, University of Canberra, Bruce, ACT, Australia
| | - Laura A Garvican-Lewis
- Mary Mackillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria, Australia.,Department of Physiology, Australian Institute of Sport, Bruce, ACT, Australia
| | - Christopher J Gore
- Department of Physiology, Australian Institute of Sport, Bruce, ACT, Australia
| | - Garth L Maker
- Separation Science and Metabolomics Laboratory, Murdoch University, Murdoch, WA, Australia.,School of Veterinary and Life Sciences, Murdoch University, Murdoch, WA, Australia
| | - Robert D Trengove
- Separation Science and Metabolomics Laboratory, Murdoch University, Murdoch, WA, Australia.,Metabolomics Australia, Murdoch University Node, Murdoch, WA, Australia
| | - Jeremiah J Peiffer
- School of Psychology and Exercise Science, Murdoch University, Murdoch, WA, Australia
| |
Collapse
|
23
|
Huang L, Zhang L, Li T, Liu YW, Wang Y, Liu BJ. Human Plasma Metabolomics Implicates Modified 9-cis-Retinoic Acid in the Phenotype of Left Main Artery Lesions in Acute ST-Segment Elevated Myocardial Infarction. Sci Rep 2018; 8:12958. [PMID: 30154509 PMCID: PMC6113282 DOI: 10.1038/s41598-018-30219-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 11/09/2017] [Accepted: 07/23/2018] [Indexed: 12/18/2022] Open
Abstract
The detection of left main coronary artery disease (LMCAD) is crucial before ST-segment elevated myocardial infarction (STEMI) or sudden cardiac death. The aim of this study was to identify characteristic metabolite modifications in the LMCAD phenotype, using the metabolomics technique. Metabolic profiles were generated based on ultra-performance liquid chromatography and mass spectrometry, combined with multivariate statistical analysis. Plasma samples were collected prospectively from a propensity-score matched cohort including 44 STEMI patients (22 consecutive LMCAD and 22 non-LMCAD), and 22 healthy controls. A comprehensive metabolomics data analysis was performed with Metaboanalyst 3.0 version. The retinol metabolism pathway was shown to have the strongest discriminative power for the LMCAD phenotype. According to biomarker analysis through receiver-operating characteristic curves, 9-cis-retinoic acid (9cRA) dominated the first page of biomarkers, with area under the curve (AUC) value 0.888. Next highest were a biomarker panel consisting of 9cRA, dehydrophytosphingosine, 1H-Indole-3-carboxaldehyde, and another seven variants of lysophosphatidylcholines, exhibiting the highest AUC (0.933). These novel data propose that the retinol metabolism pathway was the strongest differential pathway for the LMCAD phenotype. 9cRA was the most critical biomarker of LMCAD, and a ten-metabolite plasma biomarker panel, in which 9cRA remained the weightiest, may help develop a potent predictive model for LMCAD in clinic.
Collapse
Affiliation(s)
- Lei Huang
- Heart Center, Tianjin Third Central Hospital, Tianjin, P.R. China.,Tianjin Institute of Hepatobiliary Disease, Tianjin, P.R. China.,Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, P.R. China
| | - Lei Zhang
- Tianjin Institute of Hepatobiliary Disease, Tianjin, P.R. China.,Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, P.R. China.,Department of Clinical Laboratory, Tianjin Third Central Hospital, Tianjin, P.R. China
| | - Tong Li
- Heart Center, Tianjin Third Central Hospital, Tianjin, P.R. China. .,Tianjin Institute of Hepatobiliary Disease, Tianjin, P.R. China. .,Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, P.R. China.
| | - Ying-Wu Liu
- Heart Center, Tianjin Third Central Hospital, Tianjin, P.R. China.,Tianjin Institute of Hepatobiliary Disease, Tianjin, P.R. China.,Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, P.R. China
| | - Yu Wang
- Heart Center, Tianjin Third Central Hospital, Tianjin, P.R. China.,Tianjin Institute of Hepatobiliary Disease, Tianjin, P.R. China.,Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, P.R. China
| | - Bo-Jiang Liu
- Heart Center, Tianjin Third Central Hospital, Tianjin, P.R. China.,Tianjin Institute of Hepatobiliary Disease, Tianjin, P.R. China.,Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, P.R. China
| |
Collapse
|
24
|
Zhu B, Cao H, Sun L, Li B, Guo L, Duan J, Zhu H, Zhang Q. Metabolomics-based mechanisms exploration of Huang-Lian Jie-Du decoction on cerebral ischemia via UPLC-Q-TOF/MS analysis on rat serum. JOURNAL OF ETHNOPHARMACOLOGY 2018; 216:147-156. [PMID: 29360497 DOI: 10.1016/j.jep.2018.01.015] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Academic Contribution Register] [Received: 10/23/2017] [Revised: 12/28/2017] [Accepted: 01/11/2018] [Indexed: 06/07/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Huang-Lian Jie-Du decoction (HLJDD), a traditional formula of Chinese medicine constituted with Rhizoma Coptidis, RadixScutellariae, CortexPhellodendri amurensis and Fructus Gardeniae, exhibits unambiguous therapeutic effect on cerebral ischemia via multi-targets action. Further investigation, however, is still required to explore the relationship between those mechanisms and targets through system approaches. MATERIALS AND METHODS Rats of cerebral ischemia were completed by middle cerebral artery occlusion (MCAO) with reperfusion. Following evaluation of pharmacological actions of HLJDD on MCAO rats, the plasma samples from rats of control, MCAO and HLJDD-treated MCAO groups were prepared strictly and subjected to ultra-performance liquid chromatography quadrupole time of flight mass spectrometry for metabolites analysis. The raw mass data were imported to MassLynx software for peak detection and alignment, and further introduced to EZinfo 2.0 software for orthogonal projection to latent structures analysis, principal component analysis and partial least-squares-discriminant analysis. The metabolic pathways assay of those potential biomarkers were performed with MetaboAnalyst through the online database, HMDB, Metlin, KEGG and SMPD. Those intriguing metabolic pathways were further investigated via biochemical assay. RESULTS HLJDD ameliorated the MCAO-induce cerebral damage and blocked the severe inflammation response. There were nineteen different biomarkers identified among control, MCAO and HLJDD-treated MCAO groups. Ten metabolic pathways were proposed from these significant metabolites. Incorporation with the biochemical assay of cerebral tissue, modulation of metabolic stress, regulation glutamate/GABA-glutamine cycle and enhancement of cholinergic neurons function were explored that involved in the actions of HLJDD on cerebral ischemia. CONCLUSION HLJDD achieves therapeutic action on cerebral ischemia via coordinating the basic pathophysiological network of metabolic stress, glutamate metabolism, and acetylcholine levels and function.
Collapse
MESH Headings
- Acetylcholine/metabolism
- Animals
- Behavior, Animal/drug effects
- Biomarkers/blood
- Brain/drug effects
- Brain/metabolism
- Brain/pathology
- Brain/physiopathology
- Chromatography, Liquid
- Disease Models, Animal
- Drugs, Chinese Herbal/pharmacology
- Energy Metabolism/drug effects
- Glutamic Acid/metabolism
- Infarction, Middle Cerebral Artery/blood
- Infarction, Middle Cerebral Artery/drug therapy
- Infarction, Middle Cerebral Artery/pathology
- Infarction, Middle Cerebral Artery/psychology
- Inflammation Mediators/blood
- Least-Squares Analysis
- Male
- Metabolomics/methods
- Multivariate Analysis
- Neuroprotective Agents/pharmacology
- Principal Component Analysis
- Rats, Sprague-Dawley
- Spectrometry, Mass, Electrospray Ionization
- Stress, Physiological/drug effects
- Time Factors
Collapse
Affiliation(s)
- Baojie Zhu
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Huiting Cao
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Limin Sun
- School of Traditional Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China.
| | - Bo Li
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Liwei Guo
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Jinao Duan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Huaxu Zhu
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Qichun Zhang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| |
Collapse
|
25
|
Liu C, Liu B, Liu L, Zhang EL, Sun BD, Xu G, Chen J, Gao YQ. Arachidonic Acid Metabolism Pathway Is Not Only Dominant in Metabolic Modulation but Associated With Phenotypic Variation After Acute Hypoxia Exposure. Front Physiol 2018; 9:236. [PMID: 29615930 PMCID: PMC5864929 DOI: 10.3389/fphys.2018.00236] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 09/19/2017] [Accepted: 03/02/2018] [Indexed: 12/22/2022] Open
Abstract
Background: The modulation of arachidonic acid (AA) metabolism pathway is identified in metabolic alterations after hypoxia exposure, but its biological function is controversial. We aimed at integrating plasma metabolomic and transcriptomic approaches to systematically explore the roles of the AA metabolism pathway in response to acute hypoxia using an acute mountain sickness (AMS) model. Methods: Blood samples were obtained from 53 enrolled subjects before and after exposure to high altitude. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and RNA sequencing were separately performed for metabolomic and transcriptomic profiling, respectively. Influential modules comprising essential metabolites and genes were identified by weighted gene co-expression network analysis (WGCNA) after integrating metabolic information with phenotypic and transcriptomic datasets, respectively. Results: Enrolled subjects exhibited diverse response manners to hypoxia. Combined with obviously altered heart rate, oxygen saturation, hemoglobin, and Lake Louise Score (LLS), metabolomic profiling detected that 36 metabolites were highly related to clinical features in hypoxia responses, out of which 27 were upregulated and nine were downregulated, and could be mapped to AA metabolism pathway significantly. Integrated analysis of metabolomic and transcriptomic data revealed that these dominant molecules showed remarkable association with genes in gas transport incapacitation and disorders of hemoglobin metabolism pathways, such as ALAS2, HEMGN. After detailed description of AA metabolism pathway, we found that the molecules of 15-d-PGJ2, PGA2, PGE2, 12-O-3-OH-LTB4, LTD4, LTE4 were significantly up-regulated after hypoxia stimuli, and increased in those with poor response manner to hypoxia particularly. Further analysis in another cohort showed that genes in AA metabolism pathway such as PTGES, PTGS1, GGT1, TBAS1 et al. were excessively elevated in subjects in maladaptation to hypoxia. Conclusion: This is the first study to construct the map of AA metabolism pathway in response to hypoxia and reveal the crosstalk between phenotypic variation under hypoxia and the AA metabolism pathway. These findings may improve our understanding of the advanced pathophysiological mechanisms in acute hypoxic diseases and provide new insights into critical roles of the AA metabolism pathway in the development and prevention of these diseases.
Collapse
Affiliation(s)
- Chang Liu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Third Military Medical University, Chongqing, China.,Key Laboratory of High Altitude Environmental Medicine, Army Medical University, Third Military Medical University, Ministry of Education, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Bao Liu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Third Military Medical University, Chongqing, China.,Key Laboratory of High Altitude Environmental Medicine, Army Medical University, Third Military Medical University, Ministry of Education, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China.,The 12th Hospital of Chinese People's Liberation Army, Kashi, China
| | - Lu Liu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Third Military Medical University, Chongqing, China.,Key Laboratory of High Altitude Environmental Medicine, Army Medical University, Third Military Medical University, Ministry of Education, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Er-Long Zhang
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Third Military Medical University, Chongqing, China.,Key Laboratory of High Altitude Environmental Medicine, Army Medical University, Third Military Medical University, Ministry of Education, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Bind-da Sun
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Third Military Medical University, Chongqing, China.,Key Laboratory of High Altitude Environmental Medicine, Army Medical University, Third Military Medical University, Ministry of Education, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Gang Xu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Third Military Medical University, Chongqing, China.,Key Laboratory of High Altitude Environmental Medicine, Army Medical University, Third Military Medical University, Ministry of Education, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Jian Chen
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Third Military Medical University, Chongqing, China.,Key Laboratory of High Altitude Environmental Medicine, Army Medical University, Third Military Medical University, Ministry of Education, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| | - Yu-Qi Gao
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Third Military Medical University, Chongqing, China.,Key Laboratory of High Altitude Environmental Medicine, Army Medical University, Third Military Medical University, Ministry of Education, Chongqing, China.,Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China
| |
Collapse
|
26
|
Liu C, Liu B, Zhang EL, Liao WT, Liu J, Sun BD, Xu G, Chen J, Gao YQ. Elevated pentose phosphate pathway is involved in the recovery of hypoxia‑induced erythrocytosis. Mol Med Rep 2017; 16:9441-9448. [PMID: 29039604 PMCID: PMC5780001 DOI: 10.3892/mmr.2017.7801] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 03/15/2017] [Accepted: 09/27/2017] [Indexed: 12/20/2022] Open
Abstract
As a typical model of hypoxia-induced excessive erythrocytosis, high altitude polycythemia (HAPC) results in microcirculation disturbance, aggravates tissue hypoxia and results in a severe clinical outcome, without any effective intervention methods except for returning to an oxygen-rich environment. The present study aimed to explore potential therapeutic targets which may participate in the recovery of HAPC by studying the mechanisms of reducing the hemoglobin (HB) concentration during re-oxygenation. A total of 14 and 13 subjects were recruited over a 5,300 m distance and 5,170 m area. The patients were classified into HAPC or control groups based on their HB value. Plasma samples were collected on the day when they finished their stay in plateau for a year, and on the 180th day following their reaching in plain. Metabolic profiling was conducted by UPLC-QTOF/MS. MetaboAnalyst platform was performed to explore the most perturbed metabolic pathways. A panel of differential metabolites were obtained in the recovery phase of HAPC and control groups. The present study identified the uniquely upregulated pentose phosphate pathway in HAPC subjects, along with a significantly decreased HB level. The findings were verified via a direct comparison between HAPC and control subjects at a high altitude. An increased pentose phosphate pathway was identified in control groups compared with HAPC subjects. An elevated pentose phosphate pathway may therefore participate in the recovery of HAPC, whereas a downregulated pentose phosphate pathway may contribute to hypoxia-induced erythrocytosis. The results of the present study provide potential therapeutic strategies and novel insights into the pathogenesis of hypoxia-induced polycythemia.
Collapse
Affiliation(s)
- Chang Liu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Bao Liu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Er-Long Zhang
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Wen-Ting Liao
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Jie Liu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Bing-Da Sun
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Gang Xu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Jian Chen
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Yu-Qi Gao
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| |
Collapse
|
27
|
Liu J, Zhan G, Chen D, Chen J, Yuan ZB, Zhang EL, Gao YX, Xu G, Sun BD, Liao W, Gao YQ. UPLC‑QTOFMS‑based metabolomic analysis of the serum of hypoxic preconditioning mice. Mol Med Rep 2017; 16:6828-6836. [PMID: 28901489 PMCID: PMC5865841 DOI: 10.3892/mmr.2017.7493] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 03/15/2017] [Accepted: 07/24/2017] [Indexed: 01/06/2023] Open
Abstract
Hypoxic preconditioning (HPC) is well‑known to exert a protective effect against hypoxic injury; however, the underlying molecular mechanism remains unclear. The present study utilized a serum metabolomics approach to detect the alterations associated with HPC. In the present study, an animal model of HPC was established by exposing adult BALB/c mice to acute repetitive hypoxia four times. The serum samples were collected by orbital blood sampling. Metabolite profiling was performed using ultra‑performance liquid chromatography‑quadrupole time‑of‑flight mass spectrometry (UPLC‑QTOFMS), in conjunction with univariate and multivariate statistical analyses. The results of the present study confirmed that the HPC mouse model was established and refined, suggesting significant differences between the control and HPC groups at the molecular levels. HPC caused significant metabolic alterations, as represented by the significant upregulation of valine, methionine, tyrosine, isoleucine, phenylalanine, lysophosphatidylcholine (LysoPC; 16:1), LysoPC (22:6), linoelaidylcarnitine, palmitoylcarnitine, octadecenoylcarnitine, taurine, arachidonic acid, linoleic acid, oleic acid and palmitic acid, and the downregulation of acetylcarnitine, malate, citrate and succinate. Using MetaboAnalyst 3.0, a number of key metabolic pathways were observed to be acutely perturbed, including valine, leucine and isoleucine biosynthesis, in addition to taurine, hypotaurine, phenylalanine, linoleic acid and arachidonic acid metabolism. The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the protective mechanism of HPC.
Collapse
Affiliation(s)
- Jie Liu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Gang Zhan
- Key Laboratory of High Altitude Medicine, Ministry of Education, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Dewei Chen
- Key Laboratory of High Altitude Medicine, Ministry of Education, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Jian Chen
- Key Laboratory of High Altitude Medicine, Ministry of Education, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Zhi-Bin Yuan
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Er-Long Zhang
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Yi-Xing Gao
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Gang Xu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Bing-Da Sun
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Wenting Liao
- Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China
| | - Yu-Qi Gao
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| |
Collapse
|
28
|
Hinkelbein J, Jansen S, Iovino I, Kruse S, Meyer M, Cirillo F, Drinhaus H, Hohn A, Klein C, Robertis ED, Beutner D. Thirty Minutes of Hypobaric Hypoxia Provokes Alterations of Immune Response, Haemostasis, and Metabolism Proteins in Human Serum. Int J Mol Sci 2017; 18:E1882. [PMID: 28858246 PMCID: PMC5618531 DOI: 10.3390/ijms18091882] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 07/27/2017] [Revised: 08/21/2017] [Accepted: 08/29/2017] [Indexed: 12/20/2022] Open
Abstract
Hypobaric hypoxia (HH) during airline travel induces several (patho-) physiological reactions in the human body. Whereas severe hypoxia is investigated thoroughly, very little is known about effects of moderate or short-term hypoxia, e.g. during airline flights. The aim of the present study was to analyse changes in serum protein expression and activation of signalling cascades in human volunteers staying for 30 min in a simulated altitude equivalent to airline travel. After approval of the local ethics committee, 10 participants were exposed to moderate hypoxia (simulation of 2400 m or 8000 ft for 30 min) in a hypobaric pressure chamber. Before and after hypobaric hypoxia, serum was drawn, centrifuged, and analysed by two-dimensional gel electrophoresis (2-DIGE) and matrix-assisted laser desorption/ionization followed by time-of-flight mass spectrometry (MALDI-TOF). Biological functions of regulated proteins were identified using functional network analysis (GeneMania®, STRING®, and Perseus® software). In participants, oxygen saturation decreased from 98.1 ± 1.3% to 89.2 ± 1.8% during HH. Expression of 14 spots (i.e., 10 proteins: ALB, PGK1, APOE, GAPDH, C1QA, C1QB, CAT, CA1, F2, and CLU) was significantly altered. Bioinformatic analysis revealed an association of the altered proteins with the signalling cascades "regulation of haemostasis" (four proteins), "metabolism" (five proteins), and "leukocyte mediated immune response" (five proteins). Even though hypobaric hypoxia was short and moderate (comparable to an airliner flight), analysis of protein expression in human subjects revealed an association to immune response, protein metabolism, and haemostasis.
Collapse
Affiliation(s)
- Jochen Hinkelbein
- Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, 50937 Cologne, Germany.
| | - Stefanie Jansen
- Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, 50937 Cologne, Germany.
| | - Ivan Iovino
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Via S. Pansini, 5-80131 Napoli, Italy.
| | - Silvia Kruse
- Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, 50937 Cologne, Germany.
| | - Moritz Meyer
- Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, 50937 Cologne, Germany.
| | - Fabrizio Cirillo
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Via S. Pansini, 5-80131 Napoli, Italy.
| | - Hendrik Drinhaus
- Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, 50937 Cologne, Germany.
| | - Andreas Hohn
- Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, 50937 Cologne, Germany.
| | - Corinna Klein
- CECAD Lipidomics & Proteomics Facilities, CECAD Research Center, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
| | - Edoardo De Robertis
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Via S. Pansini, 5-80131 Napoli, Italy.
| | - Dirk Beutner
- Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, 50937 Cologne, Germany.
| |
Collapse
|
29
|
Liu C, Chen J, Liu B, Liao WT, Liu J, Xu G, Sun BD, Zhang EL, Gao YQ. Activated corticosterone synthetic pathway is involved in poor responses to re-oxygenation after prolonged hypoxia. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2017; 10:8414-8423. [PMID: 31966693 PMCID: PMC6965453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Academic Contribution Register] [Received: 05/12/2017] [Accepted: 06/20/2017] [Indexed: 06/10/2023]
Abstract
Diverse response patterns to re-oxygenation lead to various physiological or pathological phenotypes, but now lack of systematic research models in vivo. High-altitude de-acclimatization syndrome (HADAS) describes systematic alterations of re-oxygenation returning to plain after a long living in high altitude. In this study, we aim at employing a comprehensive metabolomics to explore the mechanisms for different reactions to re-oxygenation based on systematic quantitation scoring methods of HADAS model. Plasma samples were collected from 22 subjects when they finished their stay in high altitude for 1 year (5300 m), returning plain for 30th day and 180th day. These participants were divided into HADAS-S or HADAS-R group based on HADAS model on the 30th day after their reaching. Metabolic profiling was performed by ultra-performance liquid chromatography-quadrupole time-of-light mass spectrometry (UPLC-QTOFMS) in conjunction with univariate and multivariate statistical analysis. A total of 20 differential metabolites were identified by the comparison between HADAS-S and HADAS-R group. Pathway analysis suggested that the most potential disturbed pathway is sterol synthesis pathway, especially corticosterone synthetic sub-pathway. These molecules detected in this pathway are detailed that they showed a rapid and significant increasing manner in HADAS-S subjects comparing to HADAS-R group in the process of re-oxygenation. In conclusion, we identified that excessive stress responses to re-oxygenation might contribute to the distinctions between HADAS-S and HADAS-R group. These findings provide novel insights for further understanding of the pathogenesis for metabolic abnormalities in re-oxygenation after prolonged hypoxia.
Collapse
Affiliation(s)
- Chang Liu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China
- Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China
- Key Laboratory of High Altitude Medicine, PLAChongqing, China
| | - Jian Chen
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China
- Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China
- Key Laboratory of High Altitude Medicine, PLAChongqing, China
| | - Bao Liu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China
- Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China
- Key Laboratory of High Altitude Medicine, PLAChongqing, China
| | - Wen-Ting Liao
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China
- Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China
- Key Laboratory of High Altitude Medicine, PLAChongqing, China
| | - Jie Liu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China
- Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China
- Key Laboratory of High Altitude Medicine, PLAChongqing, China
| | - Gang Xu
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China
- Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China
- Key Laboratory of High Altitude Medicine, PLAChongqing, China
| | - Bing-Da Sun
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China
- Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China
- Key Laboratory of High Altitude Medicine, PLAChongqing, China
| | - Er-Long Zhang
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China
- Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China
- Key Laboratory of High Altitude Medicine, PLAChongqing, China
| | - Yu-Qi Gao
- Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical UniversityChongqing, China
- Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of EducationChongqing, China
- Key Laboratory of High Altitude Medicine, PLAChongqing, China
| |
Collapse
|
30
|
Šket R, Treichel N, Debevec T, Eiken O, Mekjavic I, Schloter M, Vital M, Chandler J, Tiedje JM, Murovec B, Prevoršek Z, Stres B. Hypoxia and Inactivity Related Physiological Changes (Constipation, Inflammation) Are Not Reflected at the Level of Gut Metabolites and Butyrate Producing Microbial Community: The PlanHab Study. Front Physiol 2017; 8:250. [PMID: 28522975 PMCID: PMC5416748 DOI: 10.3389/fphys.2017.00250] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 10/25/2016] [Accepted: 04/10/2017] [Indexed: 12/12/2022] Open
Abstract
We explored the assembly of intestinal microbiota in healthy male participants during the run-in (5 day) and experimental phases [21-day normoxic bed rest (NBR), hypoxic bedrest (HBR)], and hypoxic ambulation (HAmb) in a strictly controlled laboratory environment, balanced fluid, and dietary intakes, controlled circadian rhythm, microbial ambiental burden, and 24/7 medical surveillance. The fraction of inspired O2 (FiO2) and partial pressure of inspired O2 (PiO2) were 0.209 and 133.1 ± 0.3 mmHg for NBR and 0.141 ± 0.004 and 90.0 ± 0.4 mmHg for both hypoxic variants (HBR and HAmb; ~4,000 m simulated altitude), respectively. A number of parameters linked to intestinal transit spanning Bristol Stool Scale, defecation rates, zonulin, α1-antitrypsin, eosinophil derived neurotoxin, bile acids, reducing sugars, short chain fatty acids, total soluble organic carbon, water content, diet composition, and food intake were measured (167 variables). The abundance, structure, and diversity of butyrate producing microbial community were assessed using the two primary bacterial butyrate synthesis pathways, butyryl-CoA: acetate CoA-transferase (but) and butyrate kinase (buk) genes. Inactivity negatively affected fecal consistency and in combination with hypoxia aggravated the state of gut inflammation (p < 0.05). In contrast, gut permeability, various metabolic markers, the structure, diversity, and abundance of butyrate producing microbial community were not significantly affected. Rearrangements in the butyrate producing microbial community structure were explained by experimental setup (13.4%), experimentally structured metabolites (12.8%), and gut metabolite-immunological markers (11.9%), with 61.9% remaining unexplained. Many of the measured parameters were found to be correlated and were hence omitted from further analyses. The observed progressive increase in two immunological intestinal markers suggested that the transition from healthy physiological state toward the developed symptoms of low magnitude obesity-related syndromes was primarily driven by the onset of inactivity (lack of exercise in NBR) that were exacerbated by systemic hypoxia (HBR) and significantly alleviated by exercise, despite hypoxia (HAmb). Butyrate producing community in colon exhibited apparent resilience toward short-term modifications in host exercise or hypoxia. Progressive constipation (decreased intestinal motility) and increased local inflammation marker suggest that changes in microbial colonization and metabolism were taking place at the location of small intestine.
Collapse
Affiliation(s)
- Robert Šket
- Department of Animal Science, Biotechnical Faculty, University of LjubljanaLjubljana, Slovenia
| | - Nicole Treichel
- Research Unit for Comparative Microbiome Analysis, Helmholtz Zentrum München - German Research Center for Environmental HealthNeuherberg, Germany
| | - Tadej Debevec
- Department of Automation, Biocybernetics and Robotics, Jozef Stefan InstituteLjubljana, Slovenia
| | - Ola Eiken
- Department of Environmental Physiology, Swedish Aerospace Physiology Centre, Royal Institute of TechnologyStockholm, Sweden
| | - Igor Mekjavic
- Department of Automation, Biocybernetics and Robotics, Jozef Stefan InstituteLjubljana, Slovenia
| | - Michael Schloter
- Research Unit for Comparative Microbiome Analysis, Helmholtz Zentrum München - German Research Center for Environmental HealthNeuherberg, Germany
| | - Marius Vital
- Center for Microbial Ecology, Michigan State UniversityEast Lansing, MI, USA
| | - Jenna Chandler
- Center for Microbial Ecology, Michigan State UniversityEast Lansing, MI, USA
| | - James M Tiedje
- Center for Microbial Ecology, Michigan State UniversityEast Lansing, MI, USA
| | - Boštjan Murovec
- Laboratory for Artificial Sight and Automation, Faculty of Electrical Sciences, University of LjubljanaLjubljana, Slovenia
| | - Zala Prevoršek
- Department of Animal Science, Biotechnical Faculty, University of LjubljanaLjubljana, Slovenia
| | - Blaž Stres
- Department of Animal Science, Biotechnical Faculty, University of LjubljanaLjubljana, Slovenia.,Center for Clinical Neurophysiology, Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
| |
Collapse
|
31
|
Kong Z, Li M, An J, Chen J, Bao Y, Francis F, Dai X. The fungicide triadimefon affects beer flavor and composition by influencing Saccharomyces cerevisiae metabolism. Sci Rep 2016; 6:33552. [PMID: 27629523 PMCID: PMC5024320 DOI: 10.1038/srep33552] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 06/16/2016] [Accepted: 08/24/2016] [Indexed: 12/13/2022] Open
Abstract
Despite the fact that beer is produced on a large scale, the effects of pesticide residues on beer have been rarely investigated. In this study, we used micro-brewing settings to determine the effect of triadimefon on the growth of Saccharomyces cerevisiae and beer flavor. The yeast growth in medium was significantly inhibited (45%) at concentrations higher than 5 mg L(-1), reaching 80% and 100% inhibition at 10 mg L(-1) and 50 mg L(-1), respectively. There were significant differences in sensory quality between beer samples fermented with and without triadimefon based on data obtained with an electronic tongue and nose. Such an effect was most likely underlain by changes in yeast fermentation activity, including decreased utilization of maltotriose and most amino acids, reduced production of isobutyl and isoamyl alcohols, and increased ethyl acetate content in the fungicide treated samples. Furthermore, yeast metabolic profiling by phenotype microarray and UPLC/TOF-MS showed that triadimefon caused significant changes in the metabolism of glutathione, phenylalanine and sphingolipids, and in sterol biosynthesis. Thus, triadimefon negatively affects beer sensory qualities by influencing the metabolic activity of S. cerevisiae during fermentation, emphasizing the necessity of stricter control over fungicide residues in brewing by the food industry.
Collapse
Affiliation(s)
- Zhiqiang Kong
- Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products Processing/Laboratory of Agro-products Quality Safety Risk Assessment, Ministry of Agriculture, Beijing 100193, P. R. China
- Functional and Evolutionary Entomology, Gembloux Agro-Bio-Tech, University of Liège, Passage des Déportés 2, 5030 Gembloux, Belgium
| | - Minmin Li
- Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products Processing/Laboratory of Agro-products Quality Safety Risk Assessment, Ministry of Agriculture, Beijing 100193, P. R. China
| | - Jingjing An
- College of Food Science, Northeast Agricultural University, Key Laboratory of Dairy Science, Ministry of Education, Harbin 150030, China
| | - Jieying Chen
- Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products Processing/Laboratory of Agro-products Quality Safety Risk Assessment, Ministry of Agriculture, Beijing 100193, P. R. China
| | - Yuming Bao
- Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products Processing/Laboratory of Agro-products Quality Safety Risk Assessment, Ministry of Agriculture, Beijing 100193, P. R. China
| | - Frédéric Francis
- Functional and Evolutionary Entomology, Gembloux Agro-Bio-Tech, University of Liège, Passage des Déportés 2, 5030 Gembloux, Belgium
| | - Xiaofeng Dai
- Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products Processing/Laboratory of Agro-products Quality Safety Risk Assessment, Ministry of Agriculture, Beijing 100193, P. R. China
| |
Collapse
|
32
|
[Not Available]. High Alt Med Biol 2016; 17:57-60. [PMID: 27281470 DOI: 10.1089/ham.2016.29010.stg] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 11/13/2022] Open
|