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Multi-omics analysis of a fatty liver model using human hepatocyte chimeric mice
Akemi Ichikawa1,2, Daiki Miki1, C Nelson Hayes3
1Department of Gastroenterology, Graduate School of Biomedical and Health Science, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Scientific Reports
|February 9, 2024
Summary
Human growth hormone (GH) treatment improved fatty liver in chimeric mice fed a high-fat diet. GH administration altered lipid metabolism and reduced fat accumulation, highlighting its therapeutic potential for non-alcoholic fatty liver disease.
Area of Science:
- Hepatology
- Metabolic research
- Animal modeling
Background:
- Human hepatocytes in chimeric mice models accumulate fat and do not respond to mouse growth hormone (GH).
- Fatty liver disease is a growing health concern, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the effect of human GH on lipid metabolism and fat accumulation in a human hepatocyte chimeric mouse model of fatty liver.
- To explore the molecular mechanisms underlying GH's action using multi-omics analyses.
Main Methods:
- Development of a fatty liver mouse model using uPA/SCID chimeric mice transplanted with human hepatocytes.
- Dietary intervention (high-fat vs. normal diet) and human GH administration.
- Multi-omics analysis including RNA-Seq, DIA proteomics, and metabolomics.
Main Results:
- High-fat diet significantly increased fatty liver, while GH administration significantly decreased it.
- GH treatment reduced triglyceride levels and was associated with altered amino acid metabolism.
- Weighted gene correlation network analysis identified IGF1 and SEMA7A as key eigengenes.
Conclusions:
- Human GH administration can ameliorate fatty liver in a chimeric mouse model, even under high-fat diet conditions.
- GH influences lipid metabolism and amino acid pathways, suggesting a potential therapeutic role in fatty liver disease.
- Multi-omics data revealed distinct molecular profiles associated with diet and GH treatment.
