ArticleDiabetes2012
Liver X receptor α is involved in the transcriptional regulation of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- A 40-year challenge to resolve clinical questions through experimental/laboratory techniques.Endocrine journal · 2025Article
- Lipid metabolism and cancer.The Journal of experimental medicine · 2021Review
- JARID1a Ablation in the Liver Alters Systemic Metabolism and Adaptation to Feeding.Cell reports · 2020Article
- Identification of the fructose transporter GLUT5 (SLC2A5) as a novel target of nuclear receptor LXR.Scientific reports · 2019Article
- Plasma Protein and MicroRNA Biomarkers of Insulin Resistance: A Network-Based Integrative -Omics Analysis.Frontiers in physiology · 2019Article
- Fat-specific protein 27 is a novel target gene of liver X receptor α.Molecular and cellular endocrinology · 2018Article
- Lipocalin-2 in Fructose-Induced Fatty Liver Disease.Frontiers in physiology · 2017Article
- Regulation of type 1 iodothyronine deiodinase by LXRα.PloS one · 2017Article
- Broad Anti-tumor Activity of a Small Molecule that Selectively Targets the Warburg Effect and Lipogenesis.Cancer cell · 2015Article
- Energy metabolism in the liver.Comprehensive Physiology · 2014Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activity of 6-phosphofructo-1-kinase is strictly controlled by fructose-2,6-bisphosphate, the level of which is regulated by another enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2/FBP2). PFK2/FBP2 is a bifunctional enzyme, having kinase and phosphatase activities, and regulates both glycolysis and gluconeogenesis. Here, we examined the hormonal regulation of the PFK2/FBP2 gene in vitro using the reporter assay, the electromobility shift assay (EMSA), and the chromatin immunoprecipitation (ChIP) assay in HuH7 cells and also using the mouse liver in vivo. We found that the transcriptional activity of the PFK2/FBP2 gene was stimulated by insulin and inhibited by cAMP and glucocorticoid. Liver X receptor (LXR) α showed a potent and specific stimulatory effect on PFK2/FBP2 gene transcription. Deletion and mutagenesis analyses identified the LXR response element (LXRE) in the 5'-promoter region of the PFK2/FBP2 gene. Binding of LXRα was confirmed by the EMSA and ChIP assay. Endogenous PFK2/FBP2 mRNA in the mouse liver was increased in the fasting/refeeding state compared with the fasting state. Altogether, PFK2/FBP2 gene transcription is found to be regulated in a way that is more similar to other glycolytic enzyme genes than to gluconeogenic genes. Furthermore, our data strongly suggest that LXRα is one of the key regulators of PFK2/FBP2 gene transcription.
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