PPAR-delta

PPAR-delta — also written PPAR-beta/delta; gene PPARD; nuclear receptor NR1C2 — is one of the three peroxisome proliferator-activated receptors. It acts as a transcription factor switched on by ligands: fatty acids and their metabolites occupy a large hydrophobic pocket, the receptor pairs with RXR as a heterodimer, and the complex binds PPAR response elements in target promoters, 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 sold exclusively as a research compound. Its development was abandoned after carcinogenicity was found in long-term rodent studies, and WADA bans it in sport. This background is an integral part of the definition and belongs in any study design that involves the compound. Research on REV-ERB agonists addresses a different nuclear receptor whose metabolic readouts partly overlap.

Related terms and material

AMPK · preclinical. Reference material: metabolic & circadian compounds. Further reading: what is cardarine (GW-501516) and PPAR and REV-ERB agonists explained.