PPAR-delta

PPAR-delta — also written PPAR-beta/delta; gene PPARD; nuclear receptor NR1C2 — belongs to the PPAR trio of nuclear receptors. It acts as a transcription factor switched on by ligands: fatty acids and related metabolites fill its roomy hydrophobic ligand site, it forms a heterodimer with RXR, and this pair docks onto PPREs in the promoters it regulates, swapping corepressors for coactivators.

Why it attracts research interest

Whereas PPAR-gamma is found mainly in fat tissue, PPAR-delta is widely expressed, above all in skeletal muscle, where it controls genes such as CPT1, PDK4 and UCP2/3 along with other components of fatty-acid oxidation. A transgenic mouse study published in 2004 described a shift toward oxidative muscle fibres, and this finding is where the lasting interest in synthetic agonists began.

GW-501516 (cardarine) is the standard synthetic agonist and is offered only as research material. Development stopped after carcinogenicity was found in long-term rodent studies, and WADA bans it in sport. That history is part of what the term means and should be reflected in every protocol that involves the compound. Research on REV-ERB agonists addresses a different nuclear receptor whose metabolic readouts partly overlap.

Related terms and material

See also AMPK and preclinical. Relevant catalogue section: compounds for metabolic and circadian research. Our articles introduce cardarine (GW-501516) and explain agonists of PPAR and REV-ERB.