Wirkungen einer PPARα-Aktivierung auf Parameter des Stoffwechsels von Lipiden, Schilddrüsenhormonen und Carnitin bei Schwein und Ratte als Modelltieren
The peroxisome proliferator-activated receptor-α (PPARα) is a member of the family of nuclear transcription factors and plays a crucial role in the regulation of lipid metabolism, ketogenesis, carbohydrate metabolism and inflammatory processes. It is well established, that fibrates and oxidized fatty acids induce peroxisome proliferation and oxidative stress in liver of rats and mice. In these proliferating species, long-term administration of fibrates cause hepatocarcinogenesis. In contrast,
... sis. In contrast, non-proliferating species, like human, primates and pig, are refractory for these effects. The aim of the first part of the present work was to investigate the effects of synthetic and natural ligands of PPARα in the pig, representing a non-proliferating species. In these studies (study 1-5), several nutritional, pharmacological and toxicological aspects could be investigated successfully. The aim of the second part of the present work was to investigate the basic mechanisms, which are responsible for the increased hepatic concentrations of carnitin, as it was observed for animals after fibrate administration or fasting in previous studies. In studies with rats (study 6-8), we could demonstrate for the first time, that activation of PPARα was accompanied by strong increased hepatic expression of OCTNs, which are responsible for the cellular carnitine uptake.