Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)

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R-HSA-400206
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Homo sapiens
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Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is the major regulator of fatty acid oxidation in the liver. PPARalpha is also the target of fibrate drugs used to treat abnormal plasma lipid levels.
PPAR-alpha is a type II nuclear receptor (its subcellular location does not depend on ligand binding). PPAR-alpha forms heterodimers with Retinoid X receptor alpha (RXR-alpha), another type II nuclear receptor. PPAR-alpha is activated by binding fatty acid ligands, especially polyunsaturated fatty acids having 18-22 carbon groups and 2-6 double bonds.
The PPAR-alpha:RXR-alpha heterodimer binds peroxisome proliferator receptor elements (PPREs) in and around target genes. Binding of fatty acids and synthetic ligands causes a conformational change in PPAR-alpha such that it releases the corepressors and binds coactivators (CBP-SRC-HAT complex, ASC complex, and TRAP-Mediator complex) which initiate transcription of the target genes.
Target genes of PPAR-alpha participate in fatty acid transport, fatty acid oxidation, triglyceride clearance, lipoprotein production, and cholesterol homeostasis.

Literature References
PubMed ID Title Journal Year
16476485 From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions

Feige, JN, Gelman, L, Michalik, L, Desvergne, B, Wahli, W

Prog Lipid Res 2006
16503871 Peroxisome proliferator-activated receptor alpha (PPARalpha) and athero-sclerosis

Gouni-Berthold, I, Krone, W

Curr Drug Targets Cardiovasc Haematol Disord 2005
10529898 Peroxisome proliferator-activated receptors: nuclear control of metabolism

Desvergne, B, Wahli, W

Endocr Rev 1999
18288277 Peroxisome proliferator activated receptors and lipoprotein metabolism

Kersten, S

PPAR Res 2008
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