Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor (NR) superfamily that respond to changes in lipid and glucose homeostasis. Three PPAR subtypes (α, β/δ and γ; NR1C1-3) have been identified in many species including humans. The manner in which PPARs regulate gene expression includes association with retinoid-X-receptor (RXR) and binding to specific response elements found on target genes. The subsequent alteration in gene expression by the PPARs is influenced by kinases, cofactors, and other tissue specific factors. Detailed examination of the structure-function of the PPARs allows for an understanding of certain polymorphisms within the human population and may also aid in the design of new therapeutic agents. The biological niches of PPARα, -β/δ and -γ are distinct, yet have many overlapping functions. PPARα is the cognate receptor for peroxisome proliferators as well as certain fatty acid and their metabolites. Through the extensive use of the PPARα-null mouse model, it is evident that this receptor plays a key role in lipid homeostasis, particularly in the fasted state. Important fatty acid oxidation enzymes, in peroxisomes and elsewhere, are regulated by PPARα. PPARγ has received much attention as the target for antidiabetic drugs, but also plays a role in responding to endogenous compounds such as prostaglandin J2. The ability of ectopically-expressed PPARγ to induce differentiation of adipocytes, macrophages, and other cells, underscores the importance of this protein in regulating cell fate and implies a role beyond fatty acid metabolism. PPARβ/δ remains a somewhat under-appreciated member of this subfamily of receptors. The endogenous ligands for PPARβ/δ are, as a group, relatively weak activators, but includes various fatty acids and metabolites. The phenotype of the PPARβ/δ-null suggests an important role in lipid homeostasis and this protein has received attention as a downstream target of growth regulatory genes, in particular in the colon. Together, the PPARs represent an important target for therapeutic and nutritional intervention due to their importance in maintaining cellular lipid homeostasis.

Original languageEnglish (US)
Title of host publicationComprehensive Toxicology
Subtitle of host publicationSecond Edition
PublisherElsevier Inc.
Number of pages23
ISBN (Print)9780080468846
StatePublished - Jan 1 2010

All Science Journal Classification (ASJC) codes

  • Medicine(all)


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