Phosphatidylcholine and PPARalpha: a relevant connection in liver disease?

The nuclear receptors known as PPARs modulate metabolic and inflammatory pathways by responding to nutritional signals through ligand activation of transcription. They are targeted by drugs in use and in development for disease therapy. No endogenous PPARalpha ligand has been identified yet; the molecule that occupies the nuclear receptor-binding site in vivo while the receptor is actively driving transcription has been presently searched for by Chakravarthy et al. The group provides now a solid evidence that endogenous lipid synthesis generates a discrete phosphatidylcholine species, 1-palmitoyl 2-oleyl phosphatidylcholine (16:0/18:1 PC), that serves as an endogenous ligand for PPARalpha.