Effects of activation of liver X receptor and peroxisome proliferator-activated receptor alpha on bile acid synthesis in rats / 中国医学科学院学报

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effects of the simultaneous activation of liver X receptor (LXR) and peroxisome proliferator-activated receptor alpha (PPARalpha) on bile acid biosynthesis in rats.</p><p><b>METHODS</b>Totally 36 male SD rats were divided into three groups with 12 rats in each group control group, high cholesterol (HC) group, and high cholesterol + fenofibrate (HC + FENO) group. Total bile acids (serum bile acids plus fecal bile acids) level was assayed. The levels of mRNA for peroxisomal palmitoyl-CoA oxidase (Acox1), LXR, cholesterol 7alpha-hydroxylase (CYP7A1), D-bifunctional protein (DBP), trihydroxycoprostanoyl-CoA oxidase (Acox2), sterol 12alpha-hydroxylase (CYP8B1), and sterol 27-hydroxylase (CYP27A1) in liver were detected by RT-PCR.</p><p><b>RESULTS</b>Total bile acid level was significantly higher in HC + FENO group than in HC group (P < 0.01), and both were significantly higher than that in control group (P < 0.01). Compared with HC group, the mRNA expression of Acox1 and DBP was significantly higher in HC + FENO group (P < 0.01), but no statistical differences was found between HC group and control group. The mRNA levels of LXR and CYP7A1 in HC + FENO group and HC group were not significantly different but were both significantly higher than that in control group (P < 0.01, P < 0.05). No changes were observed in Acox2, CYPSB1, and CYP27A1 mRNA levels among these three groups.</p><p><b>CONCLUSION</b>Simultaneous activation of LXR and PPARalpha can increase of CYP7A1 and DBP mRNA exDression and thus accelerates the biosynthesis of bile acid.</p>