Comparative transcriptional network modeling of three PPAR-α/γ co-agonists reveals distinct metabolic gene signatures in primary human hepatocytes.

ABSTRACT:

Aims

To compare the molecular and biologic signatures of a balanced dual peroxisome proliferator-activated receptor (PPAR)-α/γ agonist, aleglitazar, with tesaglitazar (a dual PPAR-α/γ agonist) or a combination of pioglitazone (Pio; PPAR-γ agonist) and fenofibrate (Feno; PPAR-α agonist) in human hepatocytes.

Methods and results

Gene expression microarray profiles were obtained from primary human hepatocytes treated with EC(50)-aligned low, medium and high concentrations of the three treatments. A systems biology approach, Causal Network Modeling, was used to model the data to infer upstream molecular mechanisms that may explain the observed changes in gene expression. Aleglitazar, tesaglitazar and Pio/Feno each induced unique transcriptional signatures, despite comparable cor

SUBMITTER: Deehan R 

PROVIDER: S-EPMC3325914 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature