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

Cheng Wang^a, Wei Zhang^a, Donghai Zhao^a, Pengyan Ji^a, Ying Chang^b, Dongfang Zhang^a, Xinyu Jiang^a, Mengxin Yu^a, Chunlian Du^b, Yuling Qiu^b, Yingxin Zhang^b, Lianhai Jin^a,*, Chunhong Sui^b,*

 
ABSTRACT:     Thisstudyaimedtoexplore 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 byWesternblotting. Quantitativeproteomicanalysiswasperformedbymassspectrometry. CIHHsignificantlyimproved 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.

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* Corresponding author, E-mail: lh_jin72@163.com, suichunhong@163.com

Received 29 Aug 2024, Accepted 0 0000