0000000000277377
AUTHOR
Sandrine Duclos
Peroxisome proliferator-activated receptor α (PPARα) activators induce hepatic farnesyl diphosphate synthase gene expression in rodents
Fibrates are hypolipidemic drugs that exert multiple effects on lipid metabolism by activating peroxisome proliferator-activated receptor alpha (PPARalpha) and modulating the expression of many target genes. In order to investigate the link between PPARalpha and cholesterol synthesis, we analysed the effect of fibrates on expression of the farnesyl diphosphate synthase (FPP synthase) gene, known to be regulated by sterol regulatory element-binding proteins (SREBPs), in conjunction with HMG-CoA reductase. In wild-type mice, both fenofibrate and WY 14,643 induced FPP synthase gene expression, an effect impaired in PPARalpha-null mice. A three-fold induction was observed in ciprofibrate-treate…
Effects of peroxisome proliferator-activated receptor alpha activation on pathways contributing to cholesterol homeostasis in rat hepatocytes
International audience; Peroxisome proliferator-activated receptor alpha (PPARa) activation by fibrates controls expression of several genes involved in hepatic cholesterol metabolism. Other genes could be indirectly controlled in response to changes in cellular cholesterol availability. To further understand how fibrates may affect cholesterol synthesis, we investigated in parallel the changes in the metabolic pathways contributing to cholesterol homeostasis in liver. Ciprofibrate increased HMG-CoA reductase and FPP synthase mRNA levels in rat hepatocytes, together with cholesterogenesis from [14C] acetate and [3H] mevalonate. The up-regulation observed in fenofibrate- and WY-14,643-treate…