Troglitazone quinone cytoplasm, PPAR-alpha, PPAR-gamma, H-Ras, Fenofibrate, TRIP2, PPAR-alpha/RXR-alpha, PtdIns(4,5)P2, Prostaglandin I2 cytoplasm, 126.96.36.199, Erk (MAPK1/3), GRB2, PI3K reg class IA, PKA-reg (cAMP-dependent), Bezafibrate, Prostaglandin H2, 188.8.131.52, 13-HPODE, TGF-beta receptor type I, COX-2 (PTGS2), MEK3(MAP2K3), SMRT, Arachidonic acid, TAK1(MAP3K7), G-protein alpha-s, p38alpha (MAPK14), RXRA, SOS, Shc, PI3K cat class IA, 15d-PGJ2, ATP cytosol, PPAR-beta(delta), XIAP, PDGF receptor, N-CoR, cAMP, AKT(PKB), Long-chain fatty acid, PTGIS, PtdIns(3,4,5)P3, MEK1(MAP2K1), IRS-1, Clofibrate, c-Raf-1, NCOA1 (SRC1), Leukotriene B4 cytoplasm, SHP, PKA-cat (cAMP-dependent), PPAR-beta(delta)/RXR-alpha, Ciprofibrate, MEK6(MAP2K6), Insulin receptor, p38 MAPK, PPAR-gamma/RXR-alpha, 15-HETE racemic, Adenylate cyclase type I, 184.108.40.206, Retinoic acid cytosol, 220.127.116.11, Linoleic acid
Peroxisome Proliferator-Activated Receptors (PPAR ) are ligand-inducible transcription factors that belong to the nuclear hormone receptor superfamily. The PPAR group consists of three types: PPAR-alpha, PPAR-beta(delta) and PPAR-gamma. They have some differences in tissue distribution, ligand and target specificity, as well as in mechanisms controlling their activity, and in processes controlled by them , , , , .
Most common intracellular ligands for all PPARs are fatty acids and eicosanoids , . Arachidonic acid was shown to activate all three types of PPARs . A lot of Long chain fatty acids activate PPAR-alpha and PPAR-beta(delta) , , . PPAR-gamma is effectively activated by polyunsaturated fatty acids, such as Linolenic acid and (all-Z)-Eicosapentaenoic acid , . Another natural PPAR-alpha activator is leukotriene B4 . One of the most important PPAR-gamma ligands is 15d-PGJ2 (15-deoxy-delta prostaglandin J2) , , . Components of oxidized low-density lipoprotein 15-HETE (15-hydroxyeicosatetraenoic acid) and 13-HODE (13-hydroxyoctadecadienoic acid) also enable the activation of PPAR-gamma. , , , . PPAR-beta(delta) is activated by prostacyclin, which is synthesized from arachidonic acid by Prostaglandin-endoperoxide synthase 2 ( COX-2 ) and Prostaglandin I2 synthase ( PTGIS ) . Moreover, many artificial PPAR ligands have been identified (for example, Fibrates for PPAR-alpha and Thiazolidinediones for PPAR-gamma ) , , , .
PPAR activity depends on many pathways, which is why these transcriptional factors are found on the crossroads of major regulatory networks. Activation of a number of growth factor receptors (for example, Platelet-derived growth factor receptor ( PDGF receptor )  ) by the specific growth factors, or activation of Insulin receptor by insulin lead to recruitment of adaptors, such as SHC transforming protein ( Shc ), Growth factor receptor-bound protein 2 ( GRB2 ) and Son of sevenless protein homologs 1 and 2 ( SOS ) that in turn activate transforming protein V-Ha-ras Harvey rat sarcoma viral oncogene homolog ( H-Ras ) and Proto-oncogene serine/threonine-protein kinase (e.g. Raf-1 ), followed by phosphorilation of Mitogen activated protein kinases 1 and 3 ( ERK ) ( . The latter kinase inhibits PPAR-alpha and PPAR-gamma , . Phosphorilation by cAMP dependent Protein kinase A ( PKA ), as well as Mitogen activated protein kinases 14 ( p38alpha ) activates PPAR-alpha. PKA-cat pathway allows PPAR-alpha to be a target of action of hormones that bind to G protein-coupled receptors and activate GNAS complex locus ( G-protein alpha-s )-dependent Adenylate cyclase ,  p38alpha -catalyzing phosphorilation of PPAR-alpha occurs as a result of MAPK cascade activity , . Activation of p38 by Mitogen-activated protein kinase kinase kinase 7 ( TAK1 )/Mitogen-activated protein kinase kinase 3 and 6 ( MKK3 and MKK6 ) cascade is followed by up-regulation of PPAR-gamma . Also, it is demonstrated that the activity of PPAR-beta(delta) and PPAR-gamma is stimulated by V-akt murine thymoma viral oncogene homolog 1 ( AKT(PKB) ) regulatory pathway , , where Phosphatidylinositol 3-kinase ( PI3K ), activated by H-Ras catalyzes the conversion of Phosphatidylinositol 4,5-biphosphate ( PtdIns(4,5)P2 ) to Phosphatidylinositol 3,4,5-triphosphate ( PtdIns(3,4,5)P3 ), which then activates AKT.
To regulate gene expression, PPAR forms a heterodimer with Retinoid X receptor alpha ( RXRA ) and this complex binds with specific DNA response element termed Peroxisome Proliferator Response Element (PPRE) , , . PPARs are able to bind a number of corepressors and coactivator proteins. mediator complex subunit 1 ( TRIP2 ) and Nuclear receptor coactivator 1 ( NCOA1 ) is shown to activate PPAR-alpha and PPAR-gamma.  Activation of PPAR-gamma is carried out also by binding with Nuclear receptor subfamily 0 group B member 2 ( SHP ) . Basic factors that suppress the activity of all three PPAR s are Nuclear receptor co-repressor ( N-CoR )  and Nuclear receptor corepressors ( SMRT ) , .
PPAR-alpha is preferentially expressed in tissues with intensive fatty acid oxidation (liver, heart, muscle, kidney and arterial wall cells) , . It is involved in fatty acid metabolism (see Map 'PPAR regulation of lipid metabolism'), lipid homeostasis, and peroxisome proliferation , , , , . There are studies also describing the role of PPAR-alpha in hepatocarcinogenesis ,  and other pathological processes , . PPAR-gamma demonstrates highest expression levels in adipose tissues . It regulates genes that participate in adipocyte differentiation, glucose and insuline homeostasis, macrophage function and inflammation , , , , , , , , . Findings involving PPAR-gamma have been useful for treatment of diseases, such as atherosclerosis and diabetes , , , , . PPAR-beta(delta) is found in many tissues , however, its phyisiological function still remains unclear , , . This factor effects expression of some genes involved in fatty acid metabolism, lipid homeostasis, skin proliferation and inflammation , ,