High-Altitude Hypoxia Exposure Induces Iron Overload and Ferroptosis in Adipose Tissue
High altitude (HA) has become one of the most challenging environments featuring hypobaric hypoxia, which seriously threatens public health, hence its gradual attraction of public attention over the past decade. The purpose of this study is to investigate the effect of HA hypoxia on iron levels, red...
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MDPI AG
2022-11-01
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| Series: | Antioxidants |
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| author | Yanfei Zhang Jinyu Fang Yingyue Dong Huiru Ding Quancheng Cheng Huaicun Liu Guoheng Xu Weiguang Zhang |
| author_facet | Yanfei Zhang Jinyu Fang Yingyue Dong Huiru Ding Quancheng Cheng Huaicun Liu Guoheng Xu Weiguang Zhang |
| author_sort | Yanfei Zhang |
| collection | DOAJ |
| description | High altitude (HA) has become one of the most challenging environments featuring hypobaric hypoxia, which seriously threatens public health, hence its gradual attraction of public attention over the past decade. The purpose of this study is to investigate the effect of HA hypoxia on iron levels, redox state, inflammation, and ferroptosis in adipose tissue. Here, 40 mice were randomly divided into two groups: the sea-level group and HA hypoxia group (altitude of 5000 m, treatment for 4 weeks). Total iron contents, ferrous iron contents, ROS generation, lipid peroxidation, the oxidative enzyme system, proinflammatory factor secretion, and ferroptosis-related biomarkers were examined, respectively. According to the results, HA exposure increases total iron and ferrous iron levels in both WAT and BAT. Meanwhile, ROS release, MDA, 4-HNE elevation, GSH depletion, as well as the decrease in SOD, CAT, and GSH-Px activities further evidenced a phenotype of redox imbalance in adipose tissue during HA exposure. Additionally, the secretion of inflammatory factors was also significantly enhanced in HA mice. Moreover, the remarkably changed expression of ferroptosis-related markers suggested that HA exposure increased ferroptosis sensitivity in adipose tissue. Overall, this study reveals that HA exposure is capable of inducing adipose tissue redox imbalance, inflammatory response, and ferroptosis, driven in part by changes in iron overload, which is expected to provide novel preventive targets for HA-related illness. |
| first_indexed | 2024-03-09T17:23:56Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T17:23:56Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-58cba49a6f714516a92a6b7bb7eabef92023-11-24T12:56:50ZengMDPI AGAntioxidants2076-39212022-11-011112236710.3390/antiox11122367High-Altitude Hypoxia Exposure Induces Iron Overload and Ferroptosis in Adipose TissueYanfei Zhang0Jinyu Fang1Yingyue Dong2Huiru Ding3Quancheng Cheng4Huaicun Liu5Guoheng Xu6Weiguang Zhang7Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, ChinaDepartment of Anatomy and Embryology, Peking University School of Basic Medical Sciences, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences and Peking University Center for Obesity and Metabolic Disease Research, Beijing 100191, ChinaDepartment of Anatomy and Embryology, Peking University School of Basic Medical Sciences, Beijing 100191, ChinaDepartment of Anatomy and Embryology, Peking University School of Basic Medical Sciences, Beijing 100191, ChinaDepartment of Anatomy and Embryology, Peking University School of Basic Medical Sciences, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences and Peking University Center for Obesity and Metabolic Disease Research, Beijing 100191, ChinaDepartment of Anatomy and Embryology, Peking University School of Basic Medical Sciences, Beijing 100191, ChinaHigh altitude (HA) has become one of the most challenging environments featuring hypobaric hypoxia, which seriously threatens public health, hence its gradual attraction of public attention over the past decade. The purpose of this study is to investigate the effect of HA hypoxia on iron levels, redox state, inflammation, and ferroptosis in adipose tissue. Here, 40 mice were randomly divided into two groups: the sea-level group and HA hypoxia group (altitude of 5000 m, treatment for 4 weeks). Total iron contents, ferrous iron contents, ROS generation, lipid peroxidation, the oxidative enzyme system, proinflammatory factor secretion, and ferroptosis-related biomarkers were examined, respectively. According to the results, HA exposure increases total iron and ferrous iron levels in both WAT and BAT. Meanwhile, ROS release, MDA, 4-HNE elevation, GSH depletion, as well as the decrease in SOD, CAT, and GSH-Px activities further evidenced a phenotype of redox imbalance in adipose tissue during HA exposure. Additionally, the secretion of inflammatory factors was also significantly enhanced in HA mice. Moreover, the remarkably changed expression of ferroptosis-related markers suggested that HA exposure increased ferroptosis sensitivity in adipose tissue. Overall, this study reveals that HA exposure is capable of inducing adipose tissue redox imbalance, inflammatory response, and ferroptosis, driven in part by changes in iron overload, which is expected to provide novel preventive targets for HA-related illness.https://www.mdpi.com/2076-3921/11/12/2367high altitudehypobaric hypoxiaadipose tissueiron overloadferrous ironferroptosis |
| spellingShingle | Yanfei Zhang Jinyu Fang Yingyue Dong Huiru Ding Quancheng Cheng Huaicun Liu Guoheng Xu Weiguang Zhang High-Altitude Hypoxia Exposure Induces Iron Overload and Ferroptosis in Adipose Tissue Antioxidants high altitude hypobaric hypoxia adipose tissue iron overload ferrous iron ferroptosis |
| title | High-Altitude Hypoxia Exposure Induces Iron Overload and Ferroptosis in Adipose Tissue |
| title_full | High-Altitude Hypoxia Exposure Induces Iron Overload and Ferroptosis in Adipose Tissue |
| title_fullStr | High-Altitude Hypoxia Exposure Induces Iron Overload and Ferroptosis in Adipose Tissue |
| title_full_unstemmed | High-Altitude Hypoxia Exposure Induces Iron Overload and Ferroptosis in Adipose Tissue |
| title_short | High-Altitude Hypoxia Exposure Induces Iron Overload and Ferroptosis in Adipose Tissue |
| title_sort | high altitude hypoxia exposure induces iron overload and ferroptosis in adipose tissue |
| topic | high altitude hypobaric hypoxia adipose tissue iron overload ferrous iron ferroptosis |
| url | https://www.mdpi.com/2076-3921/11/12/2367 |
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