Effect of chenodeoxycholic acid and ursodeoxycholic acid administration on acyl-CoA: cholesterol acyltransferase activity in human liver.
In order to investigate the relationship between bile acid pool composition and hepatic cholesterol metabolism in humans, we studied the effect of chronic feeding of chenodeoxycholic (CDCA) or ursodeoxycholic acid (UDCA) on the hepatic activity of acyl-CoA: cholesterol acyltransferase (ACAT) evaluated "in vitro". Twenty-eight gallstone patients were admitted to the study: 15 were untreated subjects, 8 were treated with UDCA (10 mg/kg/day for 15-20 days) and 5 were treated with CDCA (15 mg/kg/day for 15-20 days). A liver specimen and a bile sample were obtained during laparotomy for elective cholecystectomy. Untreated subjects had bile supersaturated with cholesterol (mean saturation index: 1.35 +/- 0.31) whereas subjects treated with either UDCA or CDCA had bile unsaturated with cholesterol (mean saturation index: 0.66 +/- 0.1 and 0.75 +/- 0.06 respectively). In all treated subjects the bile acid administered became predominant in bile. ACAT activity was 14% lower in subjects treated with UDCA and 16% lower in those treated with CDCA compared to controls; the differences did not achieve statistical significance. Microsomal cholesterol content did not differ between the groups (75.4 +/- 7.2 nmol/mg protein in control group; 86.5 +/- 7.0 nmol/mg protein in CDCA treated group; 83.4 +/- 7.0 nmol/mg protein in UDCA treated group). Our data show that the cholesterol esterifying activity of human liver is not affected by changes in bile acid pool composition.
Abate
N
N
Istituto di Patologia Medica, Università di Modena, Italy.
Carubbi
F
F
Bozzoli
M
M
Bertolotti
M
M
Farah
I
I
Rosi
A
A
Carulli
N
N
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001646:Bile / Q000378:metabolism; D002635:Chenodeoxycholic Acid / Q000378:metabolism / Q000627:therapeutic use*; D002769:Cholelithiasis / Q000188:drug therapy / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008875:Middle Aged; D002785:Sterol O-Acyltransferase / Q000378:metabolism*; D014580:Ursodeoxycholic Acid / Q000378:metabolism / Q000627:therapeutic use*
D000214:Acyl Coenzyme A; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; D002784:Cholesterol; D002785:Sterol O-Acyltransferase