Leukotriene B4 is a physiologically relevant endogenous peroxisome proliferator-activated receptor-alpha agonist.

ABSTRACT: Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that play central roles in metabolism and inflammation. Although a variety of compounds have been shown to activate PPARs, identification of physiologically relevant ligands has proven difficult. In silico studies of lipid derivatives reported here identify specific 5-lipoxygenase products as candidate physiologically relevant PPAR-alpha activators. Subsequent studies show both in vitro and in a murine model of inflammation that 5-lipoxygenase stimulation induces PPAR-alpha signaling and that this results specifically from production of the inflammatory mediator and chemoattractant leukotriene B(4) (LTB(4)). Activation of PPAR-alpha is a direct effect of intracellularly generated LTB(4) binding to the nuc

SUBMITTER: Narala VR 

PROVIDER: S-EPMC2903376 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature