Integrative and systemic approaches for evaluating PPAR?/? (PPARD) function.

ABSTRACT: The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that function as transcription factors regulating the expression of genes involved in cellular differentiation, development, metabolism and also tumorigenesis. Three PPAR isotypes (?, ?/? and ?) have been identified, among which PPAR?/? is the most difficult to functionally examine due to its tissue-specific diversity in cell fate determination, energy metabolism and housekeeping activities. PPAR?/? acts both in a ligand-dependent and -independent manner. The specific type of regulation, activation or repression, is determined by many factors, among which the type of ligand, the presence/absence of PPAR?/?-interacting corepressor or coactivator complexes and PPAR?/? protein post-translational modifications play major roles. Recently, new global approaches to the study of nuclear receptors have made it possible to evaluate their molecular activity in a more systemic fashion, rather than deeply digging into a single pathway/function. This systemic approach is ideally suited for studying PPAR?/?, due to its ubiquitous expression in various organs and its overlapping and tissue-specific transcriptomic signatures. The aim of the present review is to present in detail the diversity of PPAR?/? function, focusing on the different information gained at the systemic level, and describing the global and unbiased approaches that combine a systems view with molecular understanding.

SUBMITTER: Giordano Attianese GM 

PROVIDER: S-EPMC4419664 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature