ArticleMolecular metabolism2015
Nuclear Factor-Y is an adipogenic factor that regulates leptin gene expression.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Nuclear Factor Y controls nutrient-adaptive epithelial growth by regulating mTOR in the Drosophila midgut.Development (Cambridge, England) · 2026Article
- Alternative Splicing of the NF-Y Subunit, NF-YA, in Neuroblastoma Phenotype Heterogeneity.Cancers · 2026Review
- Adipogenesis Under Leptin Control: Mechanisms and Model-Specific Effects.International journal of molecular sciences · 2026Review
- A Novel mechanism for depot-specific leptin gene expression regulation and its persistence after weight loss.iScience · 2026Article
- Article
- Father's adolescent body silhouette is associated with offspring asthma, lung function and BMI through DNA methylation.Communications biology · 2025Article
- The role(s) of NF-Y in development and differentiation.Cell death and differentiation · 2025Review
- MCRS1 sensitizes T cell-dependent immunotherapy by augmenting MHC-I expression in solid tumors.The Journal of experimental medicine · 2024Article
- Erythropoietin regulates energy metabolism through EPO-EpoR-RUNX1 axis.Nature communications · 2024Article
- miRNA and leptin signaling in metabolic diseases and at extreme environments.Pharmacology research & perspectives · 2024Review
- DNA methylation analysis identifies key transcription factors involved in mesenchymal stem cell osteogenic differentiation.Biological research · 2023Article
- The Role of Adipocyte Endoplasmic Reticulum Stress in Obese Adipose Tissue Dysfunction: A Review.International journal of general medicine · 2023Review
- Recent progress on action and regulation of anorexigenic adipokine leptin.Frontiers in endocrinology · 2023Review
- Leptin and Asthma: What Are the Interactive Correlations?Biomolecules · 2022Review
- Transcriptome sequencing of 3,3',4,4',5-Pentachlorobiphenyl (PCB126)-treated human preadipocytes demonstrates progressive changes in pathways associated with inflammation and diabetes.Toxicology in vitro : an international journal published in association with BIBRA · 2022Article
- Genome-wide analysis of cis-regulatory changes underlying metabolic adaptation of cavefish.Nature genetics · 2022Article
- Integrative Analysis Between Genome-Wide Association Study and Expression Quantitative Trait Loci Reveals Bovine Muscle Gene Expression Regulatory Polymorphisms Associated With Intramuscular Fat and Backfat Thickness.Frontiers in genetics · 2022Article
- The transcription factor NF-Y participates to stem cell fate decision and regeneration in adult skeletal muscle.Nature communications · 2021Article
- Article
- Optimization of adipogenic differentiation conditions for canine adipose-derived stem cells.Journal of veterinary science · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveLeptin gene expression is highly correlated with cellular lipid content in adipocytes but the transcriptional mechanisms controlling leptin expression in vivo are poorly understood. In this report, we set out to identify cis- and trans-regulatory elements controlling leptin expression.
methodsLeptin-BAC luciferase transgenic mice combining with other computational and molecular techniques were used to identify transcription regulatory elements including a CCAAT-binding protein Nuclear Factor Y (NF-Y). The function of NF-Y in adipocyte was studied in vitro with 3T3-L1 cells and in vivo with adipocyte-specific knockout of NF-Y.
resultsUsing Leptin-BAC luciferase mice, we showed that DNA sequences between -22 kb and +8.8 kb can confer quantitative expression of a leptin reporter. Computational analysis of sequences and gel shift assays identified a 32 bp sequence (chr6: 28993820-2899385) consisting a CCAAT binding site for Nuclear Factor Y (NF-Y) and this was confirmed by a ChIP assay in vivo. A deletion of this 32 bp sequence in the -22 kb to +8.8 kb leptin-luciferase BAC reporter completely abrogates luciferase reporter activity in vivo. RNAi mediated knockdown of NF-Y interfered with adipogenesis in vitro and adipocyte-specific knockout of NF-Y in mice reduced expression of leptin and other fat specific genes in vivo. Further analyses of the fat specific NF-Y knockout revealed that these animals develop a moderately severe lipodystrophy that is remediable with leptin therapy.
conclusionsThese studies advance our understanding of leptin gene expression and show that NF-Y controls the expression of leptin and other adipocyte genes and identifies a new form of lipodystrophy.
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