ArticleNature communications2023
Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 144 citations in OpenAlex.
- From RCT to mechanistic study: ATRA reverses myofibroblast activation by reprogramming glucose metabolism via HIC1 and PCK1/2 to attenuate hypertrophic scar formation.Military Medical Research · 2026Trial
- Integrating bulk and single-cell RNA sequencing with GWAS reveals regulatory networks underpinning complex traits in beef cattle.Journal of animal science and biotechnology · 2026Article
- DNMT1 facilitates the progression of metabolic dysfunction-associated steatotic liver disease by impeding transcription mediated by HNF4α and PPARα.Clinical and molecular hepatology · 2026Article
- Hepatic p38γ exacerbates acetaminophen‑induced acute liver injury via PI3K/Akt‑dependent mechanisms.International journal of molecular medicine · 2026Article
- Zeaxanthin Modulates Early Metabolic and Inflammatory Responses in db/db Mice: Associations with Intestinal Lipid Handling and Gut Microbiome Remodeling.Biomolecules · 2026Article
- Aspirin Eugenol Ester Ameliorates Fatty Liver Hemorrhagic Syndrome in Laying Hens by Reducing Oxidative Stress and Inflammation.International journal of molecular sciences · 2026Article
- Omics in heat stress in poultry: implications for immune responses, proteomic changes, and nutritional strategies.Veterinary research communications · 2026Review
- Identification of central regulators related to residual feed intake in Huainan chickens based on weighted gene co-expression network analysis.Poultry science · 2026Article
- Hepatic Gluconeogenesis and the Antidepressant Effects of Exercise: A Narrative Review.Metabolites · 2026Review
- Mechanism exploration of di(2-ethylhexyl) phthalate (DEHP)-induced hepatocellular carcinoma via network toxicology and molecular docking analysis.Discover oncology · 2026Article
- Article
- Hepatotoxic Mechanisms of Polyethylene Terephthalate Microplastics Revealed by Network Toxicology, Molecular Docking, and In Vivo Validation.International journal of molecular sciences · 2026Article
- P5CS-coupled proline metabolism manipulates metabolic dysfunction-associated steatotic liver disease.Life metabolism · 2026Article
- Microglial GPR35 Ameliorates Epileptogenesis and Neuroinflammation via PDGFA Domain 2 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- AIBP deficiency drives MAFLD advancement via ITGβ3 mediated lipid metabolism disruption and pro-inflammatory activation.Cell communication and signaling : CCS · 2026Article
- Network toxicology study and key target validation of chlorpyrifos-induced nonalcoholic fatty liver disease.Scientific reports · 2026Article
- Qushi Huoxue ointment ameliorates metabolic associated steatotic liver disease through autophagy activation and ferroptosis inhibition.World journal of hepatology · 2026Article
- Deletion of RhoGDI Protects Against Hepatic Steatosis via Improved Mitochondrial Metabolism in Mice.International journal of molecular sciences · 2026Article
- METTL3 regulates Leydig cell proliferation via miR-145-PCK1 mediated gluconeogenesis in goats.Journal of animal science and biotechnology · 2026Article
- Enhanced nuclear localization of small heterodimer partner in metabolic dysfunction-associated steatohepatitis.JHEP reports : innovation in hepatology · 2026Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic associated fatty liver disease (MAFLD) encompasses a broad spectrum of hepatic disorders, including steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis. We demonstrated that phosphoenolpyruvate carboxykinase 1 (PCK1) plays a central role in MAFLD progression. Male 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 male 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. Hepatic PCK1 deficiency may be important in hepatic steatosis and fibrosis development through paracrine secretion of PDGF-AA in male mice, highlighting a potential therapeutic strategy for MAFLD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.