Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Novel Transcriptome Profiling Analyses Demonstrate that Selective PPARg Modulators Display Attenuated and Selective Gene Regulatory Activity in Comparison with PPARg Full Agonists


ABSTRACT: We conducted extensive transcriptome profiling studies to characterize 70 SPPARgMs and seven PPARg full agonists in 3T3-L1 adipocytes, and a subset of these ligands in adipose tissue of diabetic db/db mice. In both cases, the SPPARgMs generated attenuated gene regulatory responses, and their gene expression signatures were more enriched in metabolic pathways that are likely to mediate anti-diabetic efficacy than those of PPARg full agonists. More importantly, our profiling results demonstrated that in both 3T3-L1 adipocytes and db/db mice, SPPARgMs regulate the expression of anti-diabetic efficacy-associated genes to a greater extent than that of adverse effect-associated genes, while PPARg full agonists regulate both gene sets proportionally. We conducted 10 independent batches of profiling experiments. Within each batch, drug treatment and pool of vehicle controls were hybridized to the Agilent two channel microarray. Generally 2-3 biological replicates for each condition.

ORGANISM(S): Mus musculus

SUBMITTER: Yejun Tan 

PROVIDER: E-GEOD-31222 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Novel transcriptome profiling analyses demonstrate that selective peroxisome proliferator-activated receptor γ (PPARγ) modulators display attenuated and selective gene regulatory activity in comparison with PPARγ full agonists.

Tan Yejun Y   Muise Eric S ES   Dai Hongyue H   Raubertas Richard R   Wong Kenny K KK   Thompson G Marie GM   Wood Harold B HB   Meinke Peter T PT   Lum Pek Yee PY   Thompson John R JR   Berger Joel P JP  

Molecular pharmacology 20120410 1


Selective peroxisome proliferator-activated receptor γ (PPARγ) modulators (SPPARγMs) have been actively pursued as the next generation of insulin-sensitizing antidiabetic drugs, because the currently marketed PPARγ full agonists, pioglitazone and rosiglitazone, have been reported to produce serious adverse effects among patients with type 2 diabetes mellitus. We conducted extensive transcriptome profiling studies to characterize and to contrast the activities of 70 SPPARγMs and seven PPARγ full  ...[more]

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