Application of the human hepatoblastoma cell lines inducibly expressing Peroxisome Proliferator-activated Receptors (PPARs)

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and commonly play an important role in the regulation of lipid homeostasis. Although three PPAR subtypes, α, δ and γ show a relatively close amino acid sequence homology, the functions of each PPAR are distinct. For example, PPARα and PPARδ induce lipid oxidation, while PPARγ activates lipid storage and adipogenesis. To analyze the detail functions of human PPARs, we previously established tetracycline- regulated human hepatoblastoma cell lines that can be induced to express each human PPAR subtype. The expression of each PPAR subtype in established cell line was tightly controlled by the concentration of doxycycline. DNA microarray analyses using these cell lines were performed with or without adding ligand and provided the important information on the PPAR target genes. Furthermore, we analyzed the 5′-flanking region of the human adipose differentiation- related protein (adrp) gene that responded to all subtypes of PPARs, and determined the functional PPRE of the human adrp gene. Here we discuss the usefulness of these cell lines. © 2007 The Pharmaceutical Society of Japan.