Hepatic cholesterol and bile acid metabolism in subjects with gallstones: comparative effects of short erm feeding of chenodeoxycholic and ursodeoxycholic acid.

N Carulli,M Ponz De Leon,F Zironi,A Pinetti,A Smerieri,R Iori,P Loria

doi:10.1016/s0022-2275(20)39837-0

Abstract

The activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and 7alpha-hydroxylase, the enzymes controlling the rate of hepatic synthesis, respectively, of cholesterol and bile acids, and the microsomal cholesterol content were evaluated in 25 patients with cholesterol gallstones and 17 subjects without gallstones. The same quantities were estimated in 16 additional patients with gallstones given chenodeoxycholic (CDCA) or ursodeoxycholic acid (UDCA) at a dose of 15 mg/kg per day in order to investigate the comparative effect of a short term (7 days) administration of the two bile acids on the hepatic sterol metabolism. As compared to the controls, subjects with gallstones exhibited a 36% decrease of 7alpha-hydroxylase (26.8 +/- 6.2 versus 41.7 +/- 4.2 pmol/min per mg protein) and a 24% increase of the microsomal cholesterol (78.7 +/- 15.3 versus 63.1 +/- 18.1 nmol/mg protein). Although higher in the gallstone patients, the activity of HMG-CoA reductase did not differ significantly in the two groups of subjects. Administration of CDCA and UDCA changed the bile acid pool composition so that the fed bile acid predominated in the bile (mean CDCA 73% and mean UDCA 54%). Bile lipid composition did not appreciably change. In the eight subjects treated with CDCA the activity of HMG-CoA reductase was reduced to 45% of the value of untreated subjects (27.9 +/- 14.5 versus 63.5 +/- 25.3 pmol/min per mg protein) whereas in the eight subjects treated with UDCA the same enzyme showed a twofold increase (123.5 +/- 20.9). In the treated groups 7alpha-hydroxylase activity was somewhat decreased but the values did not differ significantly from those of the untreated subjects. Microsomal cholesterol content decreased with CDCA (64.8 +/- 11.6 nmol/mg protein) as well as with UDCA (59.1 +/- 10.1) treatment; however in the latter the difference attained statistical significance (P < 0.05). Altogether the results would suggest that in the liver of patients with gallstones the conversion of cholesterol to bile acids is somewhat reduced, and that changing the bile acid pool composition, by exogenous bile acid feeding, has disparate effects on hepatic cholesterol synthesis. The findings could represent the acute changes produced by bile acid feeding, however they could imply that the effects of two bile acids in dissolving cholesterol gallstones might not be related only to the changes in hepatic sterol metabolism.-Carulli, N., M. Ponz De Leon, F. Zironi, A. Pinetti, A. Smerieri, R. Iori, and P. Loria. Hepatic cholesterol and bile acid metabolism in subjects with gallstones: comparative effects of short term feeding of chenodeoxycholic and ursodeoxycholic acid.

Highlights

) administration of the two bile acids on the hepaticsterol metabolism. .4s compared to thecontrols, subjects with gallstones exhibited a 36%decrease of 7a-hydroxylase (26.8 ~f6: .2 versus 41.7 ~f4: .2 pmol/min per m g protein) and a 24% increase of the microsomal cholesterol (78.7 ? 15.3 versus 63.1 18.1 nmolimgprotein).Althoughhigher in the gallstone patients, the activity of HMG-CoA reductase did not differ significantly in the two groups ofsubjects
* contendt ecreased with CDCA (64.8 & 11.6 nmolimg protein)as well as with ursodeoxycholic acid (UDCA) (59.1 10.1) treatment; i n thelatterthedifferenceattained statistical significance (P < 0.05)A. ltogethetrhe results would suggest that in the liver of patients with gallstones the conversion of cholesterolto bile acids is somewhat reduced, andthact hangingthe bile acid pool composition, by exogenous bile acid feeding, has disparate effects on hepatic cholesterol synthesis.T h e findings couldrepresent the acute changes produced by bile acid feeding, they could imply thathe effectos f two bile acids in dissolving cholesterolgallstones mightnot be related only tothe changes in hepatic sterol metabolism.-Carulli, N., M
Our results showed that short term administration of the twobile acids haddisparateeffectsonthe cholesterol synthesis althougbhotrheducetdhe hepatic cholesterol content

Summary

Introduction

) administration of the two bile acids on the hepaticsterol metabolism. .4s compared to thecontrols, subjects with gallstones exhibited a 36%decrease of 7a-hydroxylase (26.8 ~f6: .2 versus 41.7 ~f4: .2 pmol/min per m g protein) and a 24% increase of the microsomal cholesterol (78.7 ? 15.3 versus 63.1 18.1 nmolimgprotein).Althoughhigher in the gallstone patients, the activity of HMG-CoA reductase did not differ significantly in the two groups ofsubjects. 15.3 versus 63.1 18.1 nmolimgprotein).Althoughhigher in the gallstone patients, the activity of HMG-CoA reductase did not differ significantly in the two groups ofsubjects. Reportedthatthe liver of patients with cholesterol gallstones exhibits an increased HMG-CoA reductase activity coupled to a decreasedactivity of 7a-hydroxylase, attracting attention to the hepatic sterol metabolism.

Results

Conclusion