Reactome | PPARA binds fibrates

PPARA binds fibrates

Stable Identifier

R-HSA-9734475

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

The peroxisome proliferator-activated receptor alpha (PPARA) is a nuclear ligand-activated transcription factor that is a key regulator of fatty acid oxidation in the liver. Target genes of PPARA participate in fatty acid transport, fatty acid oxidation, triglyceride clearance, lipoprotein production, and cholesterol homeostasis. Its activation mediates lipid, glucose and amino acid homeostasis.

Fibrate drugs are derivatives of fibric acid which act as PPARA agonists and are widely used to lower triglycerides, LDL-cholesterol, total-cholesterol and apolipoprotein C3 (Grundy & Vega 1987, Clavey et al. 1999) while increasing HDL-cholesterol concentrations in serum. They are used to treat hypercholesterolemia, dyslipidemia and hypertriglyceridemia (Katsiki et al. 2013, Laufs et al. 2020). Fibrate drugs include gemfibrozil (De Filippis et al. 2011), bezafibrate (Inoue et al. 2002), cipofibrate (Quang et al. 2012), clofibrate (Henke et al. 1998) and fenofibrate (Caldwell 1989).

Literature References

PubMed ID	Title	Journal	Year
10494028	Cell culture conditions determine apolipoprotein CIII secretion and regulation by fibrates in human hepatoma HepG2 cells Copin, C, Staels, B, Fruchart, J, Dallongeville, J, Mariotte, MC, Baugé, E, Clavey, V, Fruchart, JC, Chinetti, G	Cell Physiol Biochem	1999
9836620	N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel series of potent antihyperglycemic and antihyperlipidemic agents Collins, JL, Brackeen, MF, Kliewer, SA, Lehmann, JM, Blanchard, SG, Brown, KK, Leesnitzer, LM, Henke, BR, Hull-Ryde, EA, Miller, JF, Kaldor, I, Willson, TM, Szewczyk, JR, Orband-Miller, LA, Cobb, JE, Harrington, WW, Oliver, W, Mook, RA, Plunket, KD, Noble, SA, Lenhard, JM, Parks, DJ, Lake, DH, Hashim, MA	J Med Chem	1998
11779144	Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB Kusama, H, Aoyagi, S, Awata, T, Hayashi, K, Katayama, S, Mastunaga, T, Tazawa, S, Komoda, T, Itoh, F, Akahane, M, Inoue, I	Biochem Biophys Res Commun	2002
21889235	Discovery of gemfibrozil analogues that activate PPARα and enhance the expression of gene CPT1A involved in fatty acids catabolism De Filippis, B, Maccallini, C, Fantacuzzi, M, Ammazzalorso, A, Giampietro, L, Giancristofaro, A, Petruzzelli, M, Amoroso, R, D'Angelo, A	Eur J Med Chem	2011
22381047	Anti-inflammatory and PPAR transactivational effects of secondary metabolites from the roots of Asarum sieboldii Tai, BH, Thao, NP, Quang, TH, Song, SB, Ngan, NT, Kiem, PV, Kim, YH, Minh, CV	Bioorg Med Chem Lett	2012
2713875	The biochemical pharmacology of fenofibrate Caldwell, J	Cardiology	1989