| Accession |
PRJCA015144 |
| Title |
Deficiency of gluconeogenic enzyme PCK1 promotes metabolic- associated fatty liver disease (MAFLD) through PI3K/AKT/PDGF axis activation |
| Relevance |
Medical |
| Data types |
Metagenome
Metagenomic assembly
Targeted loci cultured
Targeted loci environmental
|
| Organisms |
Mus
|
| Description |
Metabolic associated fatty liver disease (MAFLD) encompasses a broad spectrum of hepatic disorders, which include steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis. We demonstrated that phosphoenolpyruvate carboxykinase 1 (PCK1) plays a central role in MAFLD progression. Mice with liver Pck1 deficiency fed a normal diet displayed hepatic lipid disorder and liver injury, whereas fibrosis and inflammation were aggravated in mice fed a high-fat diet with drinking water containing fructose and glucose (HFCD-HF/G). Forced expression of hepatic PCK1 by adeno-associated virus ameliorated MAFLD in mice. PCK1 deficiency stimulated lipogenic gene expression and lipid synthesis. Moreover, loss of hepatic PCK1 activated the RhoA/PI3K/AKT pathway by increasing intracellular GTP levels, increasing secretion of platelet-derived growth factor-AA (PDGF-AA), and promoting hepatic stellate cell activation. Treatment with RhoA and AKT inhibitors or gene silencing of RhoA or AKT1 alleviated MAFLD progression in vivo. |
| Sample scope |
Monoisolate |
| Release date |
2023-02-22 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
| 36918564
|
Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice
|
Nature Communications
|
10.1038/s41467-023-37142-3
|
2023
|
|
|
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| National Natural Science Foundation of China (NSFC)
|
|
82272975
|
|
|
|
| Submitter |
yi
liu (952354937@qq.com)
|
| Organization |
cqmu |
| Submission date |
2023-02-22 |
