TABLE 1

PPARα

Receptor nomenclature NR1C1
Receptor code 4.10.1:FA:1:C1
Molecular information Hs: 468aa, Q07869, chr. 22q13.311
Rn: 468aa, P37230, chr. 7q342
Mm: 468aa, P23204, chr. 15 E23
DNA binding
   Structure Heterodimer, RXR partner
   HRE core sequence AACTAGGNCA A AGGTCA (DR-1, DR-2)
Partners RXR (physical, functional) DNA binding4
Agonists GW409544 (8.7), LY-518674 (7.6), LY-510929 (7.55), TZD18 (7.55), LTB4 (7), oleylethanolamide (6.92), LY-465608 (6.8), pirinixic acid (6.22), fatty acids (6), ragaglitazar (6), AD-5061 (5.55), fenofibric acid (4.46) [pIC50]5–22; GW7647 (8.22), GW9578 (7.3), TAK-559 (7.17), KRP-297/MK-0767 (6.8), eicosatetraenoic acid (6.7), farglitazar (6.35), reglitazar (5.72), DRF 2519 (∼5), pristanic acid (4.4), bezafibrate (4.3), clofibrate (4.25) [pEC50]6,13,14,18,23–33; KRP-297/MK-0767 (7.64), 8S-HETE (7), GW2331 (6.8), NS-220* (6.73), [3H]AD-5061* (5.5) [pKd]9,17,18,34–38; pterostilbene, tetradecylglycidic acid, ortylthiopropionic acid39,40
Antagonists MK886 (4.6) [pIC50]41
Coactivators PPARBP, NCOA6, BFE, CREBBP, CITED2, NCOA1, NCOA3, SWI2/SNF2, PGC-1α, PPARGC1B42–52
Corepressors NRIP1, NCOR139,53–57
Biologically important isoforms PPARα {Hs, Mm, Rn}: encoded by eight exons1–3, 58; PPARαtr (truncated) {Hs}: lacks exon 6, truncated protein lacking part of hinge region and LBD, dominant-negative, 20–50% of total PPARα mRNA, not detected in rodents59
Tissue distribution Very active peroxisomal β-oxidation tissues; liver, brown fat, kidney, heart, skeletal muscle, large intestine {Hs, Mm, Rn} [Northern blot, Q-PCR, in situ hybridization, immunohistology]39
Main target genes Activated: liver fatty acid binding protein39,60, Acyl-CoA oxidase {Rn}61,62, bifunctional enzyme {Rn}61, CPTI {Hs}63–65, MCAD {Rn}66, FIAF {Mm}67, FATP {Mm}68, apolipoprotein A-II {Mm}69, G0/G1 switch gene 2 (G0S2) {Mm}70
Mutant phenotype Hypothermia and hypoglycemia upon fasting, reduced insulin resistance, prolonged inflammatory reaction, transient delay in skin healing, resistance to fibrate-induced cancer {Mm} [knockout]7,71–76; overexpression in the heart leads to cardiac insulin resistance associated with defects in insulin signaling and STAT3 activity, reduced heart function {Mm} [transgenesis]77,78; overexpression in muscle leads to the development of glucose intolerance, increased fatty acid oxidation rates, reduced AMP-activated protein kinase activity, reduced insulin-stimulated glucose uptake, repression of GLUT4 gene {Mm} [transgenesis]79; PPARαΔ13: dominant-negative mutant results in transient-impaired wound-healing and impaired inflammatory phase {Mm} [transgenesis]80
Human disease Arteriosclerosis81,82

  • aa, amino acids; chr., chromosome; HRE, hormone response element; HETE, hydroxyeicosatetraenoic acid; Q-PCR, quantitative polymerase chain reaction; FIAF, fasting-induced adipose factor; BFE, bifunctional enzyme; CREBBP, cAMP response element binding protein binding protein; CPTI, carnitine palmitoyl transferase; MCAD, medium-chain acyl-CoA dehydrogenase; FATP, fatty acid transport protein

  • ↵* Radioligand

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