Triiodothyronine (T3) response in liver of FGF21 knockout mice
Transcriptomics Dataset
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General Information
AccessionGSE58062
TitleTriiodothyronine (T3) response in liver of FGF21 knockout mice
DescriptionThyroid hormone (TH) influences metabolic pathways by binding to specific receptors (TRs), which are conditional transcription factors. T3 works through TRs to induce fibroblast growth factor (FGF) 21, a peptide hormone that is usually induced in fasting and influences lipid and carbohydrate metabolism via local hepatic and systemic endocrine effects. While administered TH and FGF21 display overlapping actions, including reductions in serum lipids, current models suggest that these hormones act independently in vivo. Here, we examined mechanisms of TH regulation of FGF21 expression and tested the possibility that FGF21 is required for induction of hepatic TH-responsive genes. We confirm that active TH (T3) and the TR selective thyromimetic GC-1 increase FGF21 transcript and peptide levels in mouse liver and that this effect requires TR. T3 also induces FGF21 in cultured hepatocytes and this effect involves direct actions of TR1, which binds a TRE within intron 2 of FGF21. Gene expression profiles in wild type and FGF21 knockout mice are highly similar indicating that FGF21 is dispensable for the majority of hepatic T3 gene responses. A small subset of genes displays diminished T3 response in the absence of FGF21. However, most of these are not obviously involved in T3-dependent hepatic lipid and carbohydrate metabolic processes. Accordingly, T3-dependent effects upon serum lipids are maintained in the FGF21-/- background. Our findings suggest that T3 regulates genes involved in classical hepatic metabolic responses independently of FGF21.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE58062
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Keyword
Dataset Accession
Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset
Filters  
Dataset Accession
Tool Name
Direction
Geneset
Small molecules which mimic FGF21 KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse FGF21 KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in FGF21 KO
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Interaction network and enrichment analysis of genes downregulated in FGF21 KO
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in FGF21 KO
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Enrichment analysis of genes downregulated in FGF21 KO
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most downregulated genes identified by...
Enrichment analysis of genes upregulated in FGF21 KO
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most upregulated genes identified by a...
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