Deficiency of gluconeogenic enzyme PCK1 promotes metabolic- associated fatty liver disease (MAFLD) through PI3K/AKT/PDGF axis activation
| Title | Deficiency of gluconeogenic enzyme PCK1 promotes metabolic- associated fatty liver disease (MAFLD) through PI3K/AKT/PDGF axis activation |
|---|---|
| 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. |
| Organism | Mus |
| Data Type | Metabolome Data by Mass Spectrometry (MS) |
| Data Accessibility | Open-access |
| BioProject | PRJCA015144 |
| Release Date | 2023-03-01 |
| Submitter | yi liu (952354937@qq.com) |
| Organization | cqmu |
| Submission Date | 2023-02-22 |
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| File ID | File Title | Number/Samples | File Type | File Size | File Suffix | Download Times | Download |
|---|---|---|---|---|---|---|---|
| OMIX003062-01 | WT-6 | 1 | Metabolome Data by Mass Spectrometry (MS) | 32.73 MB | wiff | 0 | |
| OMIX003062-02 | WT-4 | 1 | Metabolome Data by Mass Spectrometry (MS) | 32.74 MB | wiff | 0 | |
| OMIX003062-03 | KO-2 | 1 | Metabolome Data by Mass Spectrometry (MS) | 31.08 MB | wiff | 0 | |
| OMIX003062-04 | WT-5 | 1 | Metabolome Data by Mass Spectrometry (MS) | 32.74 MB | wiff | 0 | |
| OMIX003062-05 | KO-5 | 1 | Metabolome Data by Mass Spectrometry (MS) | 30.7 MB | wiff | 0 | |
| OMIX003062-06 | WT-3 | 1 | Metabolome Data by Mass Spectrometry (MS) | 32.92 MB | wiff | 0 | |
| OMIX003062-07 | WT-2 | 1 | Metabolome Data by Mass Spectrometry (MS) | 32.44 MB | wiff | 0 | |
| OMIX003062-08 | WT-1 | 1 | Metabolome Data by Mass Spectrometry (MS) | 31.02 MB | wiff | 0 | |
| OMIX003062-09 | KO-3 | 1 | Metabolome Data by Mass Spectrometry (MS) | 30.39 MB | wiff | 0 | |
| OMIX003062-10 | KO-6 | 1 | Metabolome Data by Mass Spectrometry (MS) | 30.93 MB | wiff | 0 | |
| OMIX003062-11 | KO-1 | 1 | Metabolome Data by Mass Spectrometry (MS) | 31.27 MB | wiff | 0 | |
| OMIX003062-12 | KO-4 | 1 | Metabolome Data by Mass Spectrometry (MS) | 30.5 MB | wiff | 0 |