Peroxisome proliferator-activated receptor-alpha gene level differently affects lipid metabolism and inflammation in apolipoprotein E2 knock-in mice

摘要

ObjectivePeroxisome Proliferator-Activated Receptorα (PPARα) is a ligand-activated transcription factor which controls lipid metabolism and inflammation. PPARα is activated by fibrates, hypolipidemic drugs used in the treatment of dyslipidemia. Previous studies assessing the influence of PPARα agonists on atherosclerosis in mice yielded conflicting results and the implication of PPARα therein has not been assessed. The human apoE2 knock-in (apoE2-KI) mouse is a model of mixed dyslipidemia, atherosclerosis and non-alcoholic steatohepatitis (NASH). The aim of this study was, using homo- and heterozygous PPARα-deficient mice, to analyze the consequences of quantitative variations of PPARα gene levels and its response to the synthetic PPARα agonist fenofibrate, on NASH and atherosclerosis in apoE2-KI mice.