ArticleDiabetologia2013
PREP1 deficiency downregulates hepatic lipogenesis and attenuates steatohepatitis in mice.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Induction of heme oxygenase-1 by Na+-H+ exchanger 1 protein plays a crucial role in imatinib-resistant chronic myeloid leukemia cells.The Journal of biological chemistry · 2015Trial
- Protective Effects of a Red Orange and Lemon Extract (RLE) on the Hepatotoxicity Induced by Ochratoxin A in Rats.Antioxidants (Basel, Switzerland) · 2024Article
- Comprehensive summary: the role of PBX1 in development and cancers.Frontiers in cell and developmental biology · 2024Review
- MicroRNA-1258 suppresses oxidative stress and inflammation in septic acute lung injury through the Pknox1-regulated TGF-β1/SMAD3 cascade.Clinics (Sao Paulo, Brazil) · 2024Article
- Resveratrol Improves Endothelial Function by A PREP1-Mediated Pathway in Mouse Aortic Endothelial Cells.International journal of molecular sciences · 2023Article
- Antioxidative Effects of Curcumin on the Hepatotoxicity Induced by Ochratoxin A in Rats.Antioxidants (Basel, Switzerland) · 2021Article
- Leptin and TGF-β1 Downregulate PREP1 Expression in Human Adipose-Derived Mesenchymal Stem Cells and Mature Adipocytes.Frontiers in cell and developmental biology · 2021Article
- Low-dose Bisphenol-A Promotes Epigenetic Changes atNutrients · 2020Article
- Sphingolipid Metabolism: New Insight into Ceramide-Induced Lipotoxicity in Muscle Cells.International journal of molecular sciences · 2019Review
- MiR-17 family-mediated regulation of Pknox1 influences hepatic steatosis and insulin signaling.Journal of cellular and molecular medicine · 2018Article
- Prep1 Deficiency Affects Olfactory Perception and Feeding Behavior by Impairing BDNF-TrkB Mediated Neurotrophic Signaling.Molecular neurobiology · 2018Article
- Prep1, A Homeodomain Transcription Factor Involved in Glucose and Lipid Metabolism.Frontiers in endocrinology · 2018Review
- A peptide antagonist of Prep1-p160 interaction improves ceramide-induced insulin resistance in skeletal muscle cells.Oncotarget · 2017Article
- Loss of the Homeodomain Transcription Factor Prep1 Perturbs Adult Hematopoiesis in the Bone Marrow.PloS one · 2015Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
aims/hypothesisThe aim of this study was to investigate the function of Prep1 (also known as Pknox1) in hepatic lipogenesis.
methodsThe hepatic lipogenesis pathway was evaluated by real-time RT-PCR and Western blot. Biochemical variables were assessed using a clinical chemistry analyser.
resultsSerum triacylglycerols and liver expression of fatty acid synthase (FAS) were significantly decreased in Prep1 hypomorphic heterozygous (Prep1 (i/+) ) mice compared with their non-hypomorphic littermates. Upstream FAS expression, phosphorylation of protein kinase C (PKC)ζ, liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) increased in Prep1 (i/+) mice, while protein and mRNA levels of the lipid phosphatase inhibitor of PKCζ, SH2-containing inositol 5'-phosphatase 2 (SHIP2), was more than 60% reduced. Consistent with these findings, HepG2 cells transfected with Prep1 cDNA exhibited increased triacylglycerol accumulation and FAS expression, with strongly reduced PKCζ, LKB1, AMPK and ACC phosphorylation. Further experiments revealed the presence of both Prep1 and its major partner Pbx1 at the Ship2 (also known as Inppl1) promoter. PBX-regulating protein 1 (PREP1) and pre-B cell leukaemia transcription factor 1 (PBX1) enhanced Ship2 transcription. The PREP1HR mutant, which is unable to bind PBX1, exhibited no effect on Ship2 function, indicating transcriptional activation of Ship2 by the PREP1/PBX1 complex. Treatment with a methionine- and choline-deficient diet (MCDD) induced steatosis in both Prep1 (i/+) and non-hypomorphic control mice. However, alanine aminotransferase increase, intracellular triacylglycerol content and histological evidence of liver steatosis, inflammation and necrosis were significantly less evident in Prep1 (i/+) mice, indicating that Prep1 silencing protects mice from MCDD-induced steatohepatitis. CONCLUSIONS/
interpretationOur results indicate that Prep1 silencing reduces lipotoxicity by increasing PKCζ/LKB1/AMPK/ACC signalling, while levels of PREP1 expression may determine the risk of steatohepatitis and its progression.
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