A global view on quantitative proteomic and metabolic analysis of rat livers under different hypoxia protocols

Hypobaric hypoxia causes altitude sickness and significantly affects human health. As of now, focusing on rats different proteomic and metabolic changes exposed to different hypoxic times at extreme altitude is blank. Our study integrated in vivo experiments with tandem mass tag (TMT)- and gas chromatography time-of-flight (GC-TOF)-based proteomic and metabolomic assessments, respectively. Male Sprague-Dawley rats were exposed to long-term constant hypoxia for 40 days or short-term constant hypoxia for three days, and their responses were compared with those of a normal control group. Post-hypoxia, serum marker assays related to lipid metabolism revealed significant increases in the levels of low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) in the liver. In contrast, high-density lipoprotein (HDL) levels were upregulated in the long-term constant hypoxia cohorts and were significantly reduced in the short-term constant hypoxia cohorts. Furthermore, metabolic pathway analysis indicated that glycerolipid and glycerophospholipid metabolisms were the most significantly affected pathways in long-term hypoxia group. Subsequently, RT-qPCR analyses were performed to corroborate the key regulatory elements, including macrophage galactose-type lectin (MGL) and Fatty Acid Desaturase 2 (FADS2). The results of this study provide new information for understanding the effects of different hypobaric hypoxia exposure protocols on protein expression and metabolism in low-altitude animals.