Peroxisome proliferator-activated receptors (alpha, delta and gamma) are ligand-activated transcription factors that are involved in multiple cellular responses. The PPARdelta subtype is the least understood of all PPAR subtypes. PPARdelta is activated by unsaturated fatty acids, PGI2, and by synthetic ligands. PPARdelta-regulated genes have not been identified and the factors that control PPARdelta expression are not known. The gene that encodes the mouse PPARdelta gene is contained in >30 kb DNA sequence and organized in eight exons, six of which encode the PPARdelta receptor. A PPARdelta-luciferase reporter containing 694 bp 5' upstream regulatory and 127 bp untranslated was introduced to primary brain cultures to begin a characterization of the DNA sequences that mediate transcriptional regulation of PPARdelta. PPARdelta-luciferase expression was 10 times higher in oligodendrocyte-containing mature cultures than in immature cultures, indicating that PPARdelta may play a role during oligodendrocyte migration, proliferation, and/or maturation.

Brown adipose tissue (BAT) hyperplasia is a fundamental physiological response to cold; it involves an acute phase of mitotic cell growth followed by a prolonged differentiation phase. Peroxisome proliferator-activated receptors (PPARs) are key regulators of fatty acid metabolism and adipocyte differentiation and may therefore mediate important metabolic changes during non-shivering thermogenesis. In the present study we have investigated PPAR mRNA expression in relation to peroxisome proliferation in rat BAT during cold acclimatization. By immunoelectron microscopy we show that the number of peroxisomes per cytoplasmic volume and acyl-CoA oxidase immunolabeling density remained constant (thus increasing in parallel with tissue mass and cell number) during the initial proliferative phase and the acute thermogenic response but increased after 14 days of cold exposure, correlating with terminal differentiation of BAT. A pronounced decrease in BAT PPAR alpha and PPAR gamma mRNA levels was found within hours of exposure to cold, which was reversed after 14 days, suggesting a role for either or both of these subtypes in the proliferation and induction of peroxisomes and peroxisomal beta-oxidation enzymes. In contrast, PPAR delta mRNA levels increased progressively during cold exposure. Transactivation assays in HIB 1B and HEK-293 cells demonstrated an adrenergic stimulation of peroxisome proliferator response element reporter activity via PPAR, establishing a role for these nuclear receptors in hormonal regulation of gene transcription in BAT.