Hepatic cholesterol metabolism in normo- and hyperlipidemic patients with cholesterol gallstones.

J Ahlberg,B Angelin,I Björkhem,K Einarsson,B Leijd

doi:10.1016/s0022-2275(20)40656-x

Abstract

In vivo studies have shown abnormalities in cholesterol and bile acid metabolism in primary hyperlipoproteinemia (HLP). The aim of the present investigation was to determine if the increased production of cholesterol in HLP type IV can be attributed to a correspondingly high level of the hepatic 3-hydroxy-3-methylglutaryl (HMG) CoA reductase activity and if the low cholic acid: chenodeoxycholic acid synthesis ratio in HLP type II is due to some hydroxylase deficiency. Liver biopsies from 26 normolipidemic and 25 hyperlipidemic (10 type IIa, 6 type IIb, and 9 type IV) patients undergoing elective cholecystectomy were assayed for HMG CoA reductase activity, 12 alpha-hydroxylase activity, and 25-hydroxylase activity. The HMG CoA reductase activity was normal in HLP type IIa and type IIb and was increased about twice HLP type IV (P less than 0.001). The 12 alpha- and 25-hydroxylase activities were normal in all groups of patients. The results are compatible with a normal cholesterol synthesis in the liver in HLP type II. A reduced 12 alpha- or 25-hydroxylase activity cannot explain the low production of cholic acid relative to chenodeoxycholic acid in this type of HLP. The elevated HMG CoA reductase activity found in the liver of type IV patients may, however, be part of the explanation for the elevated synthesis of cholesterol often seen in these patients.

Highlights

In vivo studies have shown abnormalities in cholesterol and bile acid metabolism in primary hyperlipoproteinemia (HLP)
The patients were not informed of their serum lipid levels until hospitalization, and thusthey had notpreviously been on any specific dietary or drug treatmenbt ecause of hyperlipidemia
The agreement of repeatedsamples was in all cases within lo%, but in three cases patients with initial hyperlipidemia were excluded because the repeated set of lipid values was within normal limits

Summary

MATERIALS AND METHODS

The presentstudycomprised26normolipidemic and 25hyperlipidemicpatients undergoing elective cholecystectomy (Table).They hadall been admitted to the outpatientclinic of the Departmentof Surgery, Serafimerlasarettet, wherethey were offered a routine laboratory health screening including determination of serum lipid levels. The patients were not informed of their serum lipid levels until hospitalization (see below), and thusthey had notpreviously been on any specific dietary or drug treatmenbt ecause of hyperlipidemia. They had not taken any other drugs affecting liver function or plasma lipids from the time of the outpatientvisit, which was at least 2 months before hospitalization. The agreement of repeatedsamples was in all cases within lo%, but in three cases patients with initial hyperlipidemia were excluded because the repeated set of lipid values was within normal limits. This was determined preoperatively in 8 of the patients with type I1 HLP and in 10 of the controls by using gas-liquid chromatography as described previously ( 1 8)

Experimental procedure

RESULTS

DISCUSSION

Findings

Methods