Metabolomic analysis of rat arterial serum under hypobaric hypoxia: Adaptive regulation of physiological systems by metabolic reprogramming

Objective

To investigate the associations between metabolic changes and functions, including energy metabolism, immune response, and redox balance, under short-term hypobaric hypoxia exposure. Non-targeted metabolomics and bioinformatics analysis were applied to explore the adaptive mechanisms of organisms in hypobaric hypoxia.

Methods

Healthy adult male Sprague—Dawley rats were placed in environments simulating altitudes of 6500 m (HC group) and 1588 m (Control group). After 14 days, arterial serum samples were analyzed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Significant metabolites (P < 0.05, VIP >1) were identified, and KEGG enrichment analysis was conducted. Differential metabolites were globally analyzed with MetaboAnalyst 5.0.

Results

A total of 117 significantly altered metabolites were identified. In the HC group, 84 metabolites significantly increased, while 33 metabolites significantly decreased compared to the Control group. KEGG enrichment analysis revealed significant metabolic pathways, including the PPAR signaling pathway, bile secretion, arginine biosynthesis, alcoholism, and cholesterol metabolism (P < 0.05). Global analysis indicated that these differential metabolites were involved in various pathways, such as energy metabolism, amino acid metabolism, nucleotide metabolism, lipid metabolism, vitamin and cofactor metabolism, steroid metabolism, neurotransmitter metabolism, and heme metabolism, all of which play crucial roles in multiple biological processes.

Conclusion

Short-term hypobaric hypoxia exposure significantly altered the metabolite profiles in the arterial serum samples of rats, revealing adaptive metabolic reprogramming in energy metabolism, redox balance, immune function, endocrine regulation, and neurological systems.