Differential effects of chronic intermittent hypobaric hypoxia on healthy and metabolic syndrome mice through liver tissue proteomic analysis

This study aimed to explore the differences in the effects of chronic intermittent hypobaric hypoxia (CIHH) on healthy and metabolic syndrome (MetS) mice through proteomic analysis of liver tissue.Male C57BL/6J mice were divided into four groups: CON (healthy mice), CIHH (healthy mice exposed to CIHH), MetS (MetS mice), and MetS+CIHH (MetS mice exposed to CIHH).Mice in the MetS and MetS+CIHH groups were used to develop a MetS model induced by a 16-week high-fat diet and 10% fructose water feeding.Then, mice in the CIHH and MetS+CIHH groups were treated with CIHH (simulating 5000-m altitude for 28 days, 6 h daily).MetS diagnostic criteria were routinely measured.Protein expression related to the hypoxia-inducible factor (HIF)-1 signaling pathway was assayed by Western blotting.Quantitative proteomic analysis was performed by mass spectrometry.CIHH significantly improved body weight, abdominal circumference, Lee's index, systolic blood pressure, fasting blood glucose, insulin resistance, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in MetS mice, while these indicators had no statistical difference in healthy mice before and after CIHH treatment.HIF-1 expression in the liver tissue was up-regulated only in MetS mice treated with CIHH.Proteomic analysis revealed disparities in the characteristics of differentially expressed proteins between healthy and MetS mice under CIHH.In summary, CIHH exhibited a significant capacity to improve MetS symptoms by up-regulating HIF-1 expression and activating multiple metabolic and signaling pathways in MetS mice.However, the effects of CIHH on healthy mice remained minimal.