Immune Microenvironmental Differences Between Obese and Healthy People in a High-Altitude Hypoxic Environment

Xiaoyan Pu,1,* Yaxuan Wang,1,* Xue Lin,2 Jun Zhao,1 Chongyang Dai,1 Yonggui Ma,3 Peijun Shi3– 5 1Medical College, Qinghai University, Xining, Qinghai Province, 810016, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610000, People’s Republic of China; 3College of Life Sciences, Qinghai Normal University, Xining, Qinghai Province, 810016, People’s Republic of China; 4State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing, 100875, People’s Republic of China; 5Faculty of Geographical Science, Beijing Normal University, Beijing, 100875, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peijun Shi, State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing, 100875, People’s Republic of China, Tel +86 10 58808179, Email spj@bnu.edu.cn Yonggui Ma, College of Life Sciences, Qinghai Normal University, Xining, Qinghai Province, 810016, People’s Republic of China, Tel +86 18697243977, Email 1261602778@qq.comPurpose: Rapid ascent to high altitudes can induce altitude illness, with obesity potentially exacerbating the hypoxic response. This study aimed to preliminarily explore the pathogenesis by comparing the immune microenvironment in obese versus normal-weight organisms after acute hypoxic exposure, and to identify potential biomarkers.Methods: Single-cell RNA sequencing was performed to profile the immune landscape following acute hypoxic injury. Animal experiments were conducted to validate key findings.Results: Single-cell analysis revealed a reduced proportion of Treg cells in obese subjects under hypoxia, suggesting a link to disease severity. This was corroborated in animal models, where obese, hypoxic rats (severely injured group) exhibited significantly fewer Treg cells compared to normal-weight, hypoxic rats (mildly injured group). Analysis of key transcription factors, including FOXP3, HIF-1α, IFN-γ, and TNF-α, showed expression trends consistent with the single-cell data.Conclusion: Our exploratory research indicates that obesity-associated impairment of Treg cell abundance and function may underlie severe hypoxic injury at high altitude. Treg cells represent a promising biomarker for risk assessment and early intervention in altitude illness.Keywords: hypoxia, single-cell sequencing, obesity, Treg cells, biomarker