Reactome | Regulation of lipid metabolism by PPARalpha

Regulation of lipid metabolism by PPARalpha

Stable Identifier

R-HSA-400206

Type

Pathway

Species

Homo sapiens

Compartment

nucleoplasm, cytosol

Synonyms

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

ReviewStatus

5/5

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Regulation of lipid metabolism by PPARalpha

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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
18288277	Peroxisome proliferator activated receptors and lipoprotein metabolism Kersten, S	PPAR Res	2008
10529898	Peroxisome proliferator-activated receptors: nuclear control of metabolism Desvergne, B, Wahli, W	Endocr Rev	1999
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