High-Altitude Condition Induces Hepatic Magnetic Susceptibility Changes and Liver Injury

Millions of people reside in hypobaric, hypoxic high-altitude environments, yet the chronic consequences of sustained exposure remain incompletely understood. Liver magnetic resonance imaging (MRI) in residents at different altitudes revealed signal alterations suggestive of changes in magnetic susceptibility and tissue composition. To further investigate these observations, mice were exposed to simulated 5000 m hypobaric hypoxia for six weeks. High-altitude-exposed mice developed significant liver impairment, characterized by increased hepatocyte apoptosis and elevated magnetic susceptibility. Quantitative analyses demonstrated approximately a two-fold increase in hepatic iron content accompanied by the formation of iron aggregates. Concomitant lipid accumulation and oxidative stress were observed, indicating coordinated disruption of iron homeostasis and metabolic balance. Collectively, these findings suggest that high-altitude-associated iron accumulation contributes to magnetic susceptibility alterations and promotes liver injury through dysregulated lipid metabolism and oxidative stress, providing mechanistic insight and potential implications for high-altitude risk assessment and clinical management.