Peroxisome proliferator-activated receptor beta or delta (PPAR-β or PPAR-δ), also known as NR1C2 (nuclear receptor subfamily 1, group C, member 2) is a nuclear receptor that in humans is encoded by the PPARD gene.[1]
This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. It was first identified in Xenopus in 1993.[2]
Contents |
PPARs are nuclear hormone receptors that bind peroxisome proliferators and control the size and number of peroxisomes produced by cells. PPARs mediate a variety of biological processes, and may be involved in the development of several chronic diseases, including diabetes, obesity, atherosclerosis, and cancer.[3][4]
This protein is a potent inhibitor of ligand-induced transcription activity of PPAR-α and PPAR-γ. It may function as an integrator of transcription repression and nuclear receptor signaling. The expression of this gene is found to be elevated in colorectal cancer cells.[5] The elevated expression can be repressed by adenomatosis polyposis coli (APC), a tumor suppressor protein involved in the APC/beta-catenin signaling pathway. Knockout studies in mice suggested the role of this protein in myelination of the corpus callosum, epidermal cell proliferation, and glucose[6] and lipid metabolism.[7]
This protein has been shown to be involved in differentiation, lipid accumulation,[8] directional sensing, polarization, and migration in keratinocytes.[9]
In one study, polymorphisms of PPARD were found to be associated with bipolar disorder.[10]
Several high affinity ligands for PPAR-δ/β have been developed, including GW 501516 and GW 0742, which play an important role in research. In one study utilizing such a ligand, it has been shown that agonism of PPAR-δ changes the body's fuel preference from glucose to lipids.[11]
PPAR-δ/β is highly expressed in colon, small intestine, liver and keratinocytes. In contrast, heart, spleen, skeletal muscle, lung, brain and thymus show low expression.[12]
Knockout mice lacking the ligand binding domain of PPAR-δ/β are viable. However these mice are smaller than the wild type both neo and postnatally. In addition, fat stores in the gonads of the mutants are smaller. The mutants also display increased epidermal hyperplasia upon induction with TPA.[13]
Several selective ligands for PPARδ are now available.
Natural ligands of PPAR-delta are metabolites of arachidonic acid, which include 4-hydroxy-2-nonenal (4-HNE) and 4-hydroxydodeca-(2E,6Z)-dienal (4-HDDE).[15][16]
Peroxisome proliferator-activated receptor delta has been shown to interact with HDAC3[17][18] and NCOR2.[18]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
|
|