[Effects of activation of liver X receptor and peroxisome proliferator-activated receptor alpha on bile acid synthesis in rats].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Simultaneous activation of LXR and PPARalpha can increase of CYP7A1 and DBP mRNA exDression and thus accelerates the biosynthesis of bile acid.
Ma
Ying
Y
Department of Biochemistry, Hebei Medical University, Shijiazhuang 050017, China.
Jiang
Ling-ling
LL
Shi
Ru-ling
RL
Liu
Jie
J
D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002784:Cholesterol / Q000494:pharmacology; D011345:Fenofibrate / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors / Q000819:agonists*; D047493:PPAR alpha / Q000819:agonists*; D051381:Rats
D001647:Bile Acids and Salts; D000960:Hypolipidemic Agents; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047493:PPAR alpha; D002784:Cholesterol; D011345:Fenofibrate