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Regulation Of Lipid Homeostasis, Inflammatory Signalling And Atherosclerosis By The Peroxisome Proliferator-Activated Receptor Delta, Lazar A. Bojic
Electronic Thesis and Dissertation Repository
The peroxisome proliferator-activated receptor (PPAR) δ is a ligand-dependent transcription factor that has been implicated in metabolic and inflammatory regulation. The molecular and physiological mechanisms by which PPARδ activation regulates lipid metabolism, inflammatory signaling and protection from atherosclerosis in states of metabolic disturbance such as insulin resistance and dyslipidemia, were investigated in a series of in vitro and in vivo studies. In vitro experiments demonstrated that PPARδ activation inhibits atherogenic lipoprotein-induced lipid accumulation and the associated proinflammatory responses. The primary mechanisms for these effects were increased fatty acid β-oxidation, decreased lipoprotein lipase (LPL) activity, reduced MAPK signaling and improved insulin ...