Human Gene Set: RUAN_RESPONSE_TO_TNF_DN

For the Mouse gene set with the same name, see RUAN_RESPONSE_TO_TNF_DN

Standard name RUAN_RESPONSE_TO_TNF_DN
Systematic name M1555
Brief description Adipocyte abundant genes down-regulated in 3T3-L1 cells (fibroblasts induced to differentiate to adipocytes) in response to TNF [GeneID=7124].
Full description or abstract Troglitazone (TGZ), a member of the thiazolidinedione class of anti-diabetic compounds and a peroxisome proliferator activator receptor-gamma (PPAR-gamma) agonist, restores systemic insulin sensitivity and improves the full insulin resistance syndrome in vivo. The mechanisms underlying its in vivo function are not understood. Here we investigated the potential functional interaction between PPAR-gamma and NF-kappaB in adipocytes. We show that TGZ selectively blocked tumor necrosis factor-alpha-induced and NF-kappaB-dependent repression of multiple adipocyte-specific genes and induction of growth phase and other genes. This occurs without interfering with NF-kappaB expression, activation, nuclear translocation, or DNA binding and without suppressing NF-kappaB-dependent survival signals. Notably, the expressions of some tumor necrosis factor-alpha-induced genes in adipocytes were unaffected by PPAR-gamma activation. In reporter gene assays in HeLa cells, ectopic expression of PPAR-gamma abolished induction of a NF-kappaB-responsive reporter gene by the p65 subunit (RelA) of NF-kappaB, and the inhibition was further enhanced in the presence of TGZ. Conversely, overexpression of p65 inhibited induction of a PPAR-gamma-responsive reporter gene by activated PPAR-gamma in a dose-dependent manner. The inhibitory effect was independent of the presence of NF-kappaB-binding sites in the promoter region. Other NF-kappaB family members, p50 and c-Rel as well as the S276A mutant of p65, blocked PPAR-gamma-mediated gene transcription less effectively. Thus, p65 antagonizes the transcriptional regulatory activity of PPAR-gamma in adipocytes, and PPAR-gamma activation can at least partially override the inhibitory effects of p65 on the expression of key adipocyte genes. Our data suggest that inhibition of NF-kappaB activity is a mechanism by which PPAR-gamma agonists improve insulin sensitivity in vivo and that adipocyte NF-kappaB is a potential therapeutic target for obesity-linked type 2 diabetes.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12732648   Authors: Ruan H,Pownall HJ,Lodish HF
Exact source Table 1: Fold-TNFa =< -1.4
Related gene sets (show 5 additional gene sets from the source publication)

(show 2 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Mus musculus
Contributed by John Newman (University of Washington)
Source platform or
identifier namespace		 MOUSE_SEQ_ACCESSION
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 79 genes
Gene families ? Categorize these 79 genes by gene family
Show members (show 85 source identifiers mapped to 79 genes)
Version history 3.1: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.