Transcriptional profiling in the livers of rats after hypobaric hypoxia exposure

Abstract

Ascent to high altitude feels uncomfortable in part because of a decreased partial pressure of oxygen due to the decrease in barometric pressure. The molecular mechanisms causing injury in liver tissue after exposure to a hypoxic environment are widely unknown. The liver must physiologically and metabolically change to improve tolerance to altitude-induced hypoxia. Since the liver is the largest metabolic organ and regulates many physiological and metabolic processes, it plays an important part in high altitude adaptation. The cellular response to hypoxia results in changes in the gene expression profile. The present study explores these changes in a rat model. To comprehensively investigate the gene expression and physiological changes under hypobaric hypoxia, we used genome-wide transcription profiling. Little is known about the genome-wide transcriptional response to acute and chronic hypobaric hypoxia in the livers of rats. In this study, we carried out RNA-Sequencing (RNA-Seq) of liver tissue from rats in three groups, normal control rats (L), rats exposed to acute hypobaric hypoxia for 2 weeks (W2L) and rats chronically exposed to hypobaric hypoxia for 4 weeks (W4L), to explore the transcriptional profile of acute and chronic mountain sickness in a mammal under a controlled time-course. We identified 497 differentially expressed genes between the three groups. A principal component analysis revealed large differences between the acute and chronic hypobaric hypoxia groups compared with the control group. Several immune-related and metabolic pathways, such as cytokine-cytokine receptor interaction and galactose metabolism, were highly enriched in the KEGG pathway analysis. Similar results were found in the Gene Ontology analysis. Cogena analysis showed that the immune-related pathways were mainly upregulated and enriched in the acute hypobaric hypoxia group.

Transcriptomic Changes in Young Japanese Males After Exposure to Acute Hypobaric Hypoxia

“…In addition to the effects of genetic polymorphisms on the physiological response to hypobaric hypoxia, transcriptional variation from a genome in an individual can provide phenotypic plasticity in response to the extreme environmental conditions, conferring acclimatization to rapid environmental changes. In recent years, transcriptomic profiles in response to hypoxic stress have been investigated in free-ranging or wild endothermic (Pan et al, 2017;Lim et al, 2019;Park et al, 2019;Qi et al, 2019) and model animals (Sharma et al, 2015;Xu et al, 2019). It is well known that hypoxic microenvironments profoundly affect cancer progression in humans (Jing et al, 2019).…”

4‐PBA inhibits hypoxia‐induced lipolysis in rat adipose tissue and lipid accumulation in the liver through regulating ER stress

“…Since the liver is the largest metabolic organ and regulates various physiological and metabolic processes, it also performs a key role in high-altitude adaptation (Xu et al, 2019). Adipose dysfunction is closely associated with metabolism-related liver diseases, an understanding of the interplay between tissues and these proposed mechanisms is still necessary (Da Silva Rosa et al, 2020).…”

Improvement of Total Flavonoids from Dracocephalum moldavica L. in Rats with Chronic Mountain Sickness through 1H-NMR Metabonomics

“…In a high-altitude environment, cellular aerobic metabolism cannot meet the demand for energy owing to insufficient oxygen supply in cells/mitochondria, hypoxic injury in cells, and an increase in the basal metabolic rate [ 8 ]. Nemkov et al [ 9 ] .…”

“…Under Evidence-Based Complementary and Alternative Medicine nonhypoxic conditions, fatty acids undergo repeated ß oxidation to generate acetyl coenzyme A (acetyl CoA), which participates in the tricarboxylic acid cycle (TCAC). In hypoxia, the oxidation of fatty acids is downregulated [8], and acetyl CoA produced from ß oxidation cannot be completely oxidized by TCAC to acetoacetic acid. Acetoacetic acid is further decomposed into acetone, ß hydroxybutyric acid, and other ketones.…”