The effects of chronic hypoxia on lipid metabolism in metabolic dysfunction-associated steatohepatitis based on transcriptomics analysis
10.19405/j.cnki.issn1000-1492.2026.08.013
- VernacularTitle:基于转录组学分析慢性低氧对代谢功能障碍相关脂肪性肝炎脂质代谢的影响
- Author:
Kang SONG
1
;
Hong LIANG
2
;
Ruyi MA
2
;
Li WANG
2
Author Information
1. Department of Endocrinology， Qinghai Provincial People's Hospital， Xining 810001
2. Medical College， Qinghai University， Xining 810016
- Publication Type:Journal Article
- Keywords:
transcriptomics;
chronic hypoxia;
metabolic dysfunction-associated steatohepatitis;
lipid;
metabolism;
differentially expressed genes
- From:
Acta Universitatis Medicinalis Anhui
2026;61(8):1431-1438
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effects of chronic hypoxic exposure on lipid metabolism in metabolic dysfunction-associated steatohepatitis mice via transcriptomic analysis. MethodsMale C57BL/6J mice were randomly divided into 3 groups： Control group （normal diet）， metabolic dysfunction-associated steatohepatitis group （MASH， high-fat diet）， hypoxic metabolic dysfunction-associated steatohepatitis group （CH-MASH， high-fat diet）. After 12 weeks， CH-MASH was given hypoxia intervention （altitude=3 800 m） for 4 weeks. Differentially expressed genes in the livers of mice from the three groups were identified using transcriptome sequencing， followed by GO and KEGG analyses. A protein-protein interaction （PPI） network was constructed to screen hub genes. Serum triglyceride （TG）， total cholesterol （TC）， and liver function parameters were measured， and hepatic histomorphological changes were observed by HE staining. ResultsSerum TG and TC significantly increased in MASH group and CH-MASH group compared with Control group. Compared to MASH group， serum TG and TC obviously increased in CH-MASH. HE staining suggested that the lipid level of CH-MASH was reduced compared with MASH. Liver transcriptomes differed markedly between CH-MASH and MASH mice. A total of 1 005 differentially expressed genes were screened. A total of 1 151 significantly enriched GO terms were obtained including extracellular regions， intrinsic components of membranes， lipid metabolism processes， small molecule metabolism processes， and small molecule synthesis processes KEGG enrichment analysis showed that DEGs were enriched in 41 pathways， including metabolic pathway， retinol metabolic pathway， PPAR signaling pathway， sterol synthesis pathway etc. In the screening protein interaction network， the closely connected genes related to lipid metabolism under hypoxia were Acaca， Hmgcs1， Acat2， Cyp51和Msmo1. The results of RT-qPCR were consistent. ConclusionChronic hypoxia significantly alters liver lipid metabolism transcription levels in MASH mice. The key genes and pathways screened in this study provide clues for further research on the mechanism of hypoxia exposure affecting liver metabolic changes in MASH mice.
