Shared PPARa/? target genes regulate brown adipocyte thermogenic function (RNA-Seq)

Purpose: To study the role of PPAR nuclear receptors in brown fat. Methods: mRNA-sequencing was performed on brown adipose tissue from mice on diets with or without added rosiglitazone or fenofibrate. Sequence reads that passed quality filters were analyzed at the transcript isoform level with RNA-Seq Unified Mapper. Results: We identified genes that were induced or repressed by either PPAR agonist, and approximately three-fold more genes were significantly regulated by rosiglitazone (rosi, a PPARg agonist) than by fenofibrate (feno, a PPARa agonist). Those genes induced by either drug were enriched for expected lipid metabolic pathways, while down-regulated genes fell in pathways of uncertain relevance. Most genes were selectively regulated by one of the two PPAR agonists, with few regulated by both. Only 34 genes were induced by both PPAR agonists (~10% of rosi-induced genes and ~25% of feno-induced genes), and these were enriched for mitochondrial functionrelated pathways, including fatty acid ß-oxidation. Conclusions: These data suggest that PPAR? agonists have stronger effects on BAT than PPARa agonists, yet those genes activated by both PPAR agonists may be particularly relevant to BAT function. Overall design: Brown adipose tissue mRNA profiles of control and PPAR agonist-treated mice were generated by deep sequencing