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

Xiaoyan Pu,Yaxuan Wang,Xue Lin,Jun Zhao,Chongyang Dai,Yonggui Ma,Peijun Shi

Published 2025 in Journal of Inflammation Research

ABSTRACT

Purpose 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.

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