PPARs

Definition: Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in lipid and glucose homeostasis, inflammation and wound healing.

Peroxisomal proliferator activated receptor gamma (PPARgamma) belongs to the family of nuclear hormone receptors (NHRs), which directly regulate transcription of target genes. The regulatory role of this receptor on lipid metabolism and insulin sensitization is well established.

Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors that regulate lipid and lipoprotein metabolism, glucose homeostasis and inflammation.

The PPAR family consists of three proteins, alpha, beta/delta and gamma. Recent data suggest that PPAR alpha and gamma activation decreases atherosclerosis progression not only by correcting metabolic disorders, but also through direct effects on the vascular wall.

The peroxisome proliferator-activated receptors (PPARs) play central roles in lipid and glucose homeostasis, cellular differentiation, and the immune/inflammatory response.

PPARs modulate the recruitment of leukocytes to endothelial cells, control the inflammatory response and lipid homeostasis of monocytes/macrophages and regulate inflammatory cytokine production by smooth muscle cells.

In addition to ligand binding, phosphorylation can regulate PPARs; the biological effects of phosphorylation depend on the stimulus, the kinase, the PPAR isotype, the residue modified, the cell type and the promoter investigated.

Cancer

The overexpression of PPARs in many human cancers has been identified.

PPARgamma activation by specific agonists leads to growth inhibition, apoptosis and differentiation of tumor cells.

PPARgamma possess evident tumor promoting properties but the receptor independent effects of its ligands compound the understanding of its biology in cancers.

Members

PPARA

PPARB

PPARC

PPARD

PPARG

Pathology

 PAX8/PPARG fusion gene in follicular thyroid tumors

See also

 PPAR signaling pathway

References

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 Das SK, Chakrabarti R. Role of PPAR in cardiovascular diseases. Recent Patents Cardiovasc Drug Discov. 2006 Jun;1(2):193-209. PMID: 18221086

 Brown JD, Plutzky J. Peroxisome proliferator-activated receptors as transcriptional nodal points and therapeutic targets. Circulation. 2007 Jan 30;115(4):518-33. PMID: 17261671

 Denning GM, Stoll LL. Peroxisome proliferator-activated receptors: potential therapeutic targets in lung disease? Pediatr Pulmonol. 2006 Jan;41(1):23-34. PMID: 16267824

 Gelman L, Michalik L, Desvergne B, Wahli W. Kinase signaling cascades that modulate peroxisome proliferator-activated receptors. Curr Opin Cell Biol. 2005 Apr;17(2):216-22. PMID: 15780600

 Evans RM, Barish GD, Wang YX. PPARs and the complex journey to obesity. Nat Med. 2004 Apr;10(4):355-61. PMID: 15057233

 Michalik L, Desvergne B, Wahli W. Peroxisome-proliferator-activated receptors and cancers: complex stories. Nat Rev Cancer. 2004 Jan;4(1):61-70. PMID: 14708026

 Yu S, Rao S, Reddy JK. Peroxisome proliferator-activated receptors, fatty acid oxidation, steatohepatitis and hepatocarcinogenesis. Curr Mol Med. 2003 Sep;3(6):561-72. PMID: 14527087

 Duval C, Chinetti G, Trottein F, Fruchart JC, Staels B. The role of PPARs in atherosclerosis. Trends Mol Med. 2002 Sep;8(9):422-30. PMID: 12223313

 Sporn MB, Suh N, Mangelsdorf DJ. Prospects for prevention and treatment of cancer with selective PPARgamma modulators (SPARMs). Trends Mol Med. 2001 Sep;7(9):395-400. PMID: 11530334

 Wada K, Nakajima A, Blumberg RS. PPARgamma and inflammatory bowel disease: a new therapeutic target for ulcerative colitis and Crohn’s disease. Trends Mol Med. 2001 Aug;7(8):329-31. PMID: 11516972