ABSTRACT
3-Hydroxybutyrate (3HB) is an important metabolite and regulatory molecule produced in liver. Previous studies have shown that 3HB could be beneficial to many diseases, including brain diseases, diabetes, and most importantly, inflammation and liver related injury. Therefore, the effect of 3HB on liver fibrosis, one key step of liver diseases which proved to be reversible, is urgent to explore. In this study, the CCl4-induced mouse model of liver fibrosis has been successfully constructed and treated by 3HB. The results demonstrate that 3HB could alleviate CCl4-induced liver injury and inflammation in mice, decrease the accumulation of collagen, the expression of pro-fibrotic genes as well as inflammatory factors, and finally the degree of liver fibrosis. The transcriptome data recovers that the anti-fibrotic effect of 3HB might be exerted through several ways, such as regulating mitochondrial function, reducing oxidative stress and p53 signaling pathways, proposing a safe and relatively fast possibility for the treatment of liver fibrosis.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Yudian Zhang: yudian_zhang{at}163.com Xinyi Liu: 13752001998{at}163.com
The revised paper changed title by specifying the title, changing anti-inflammatory effect to downstream regulation of mitochondrial fission and reduction of oxidative stress. The abstract and manuscript was updated correspondingly.
ABBREVIATIONS
- ALT
- Alanine aminotransferase
- AST
- Aspartate transaminase
- α-SMA
- Alpha smooth muscle actin
- BDH1
- 3-Hydroxybutyrate dehydrogenase
- 1,3-BDO
- 1,3-Butanediol
- BP
- Biological processes
- CC
- Cellular component
- CCl4
- Carbon tetrachloride
- ECM
- Extracellular matrix
- GO
- Gene ontology
- HCC
- Hepatocellular carcinoma
- HDL-C
- High-density lipoprotein cholesterol
- 3HB
- 3-Hydroxybutyrate
- H&E
- Hematoxylin and eosin staining
- IL-1β
- Interleukin 1β
- KEGG
- Kyoto encyclopedia of genes and genomes
- LDL-C
- Low-density lipoprotein cholesterol
- MF
- Molecular function
- NAFLD
- Non-alcoholic fatty liver disease
- NASH
- Nonalcoholic steatohepatitis
- NLRP3
- NOD-like receptor family: pyrin domain: containing 3
- ROS
- Reactive oxygen species
- TBIL
- Total bilirubin
- TG
- Total triglycerides
- TCHO
- Total cholesterol
- TNFα
- Tumor necrosis factor α
- TGF-β
- Transforming growth factor β