Journal of Lipid Research, Vol 36, 1544-1556, Copyright © 1995 by Lipid Research, Inc.
Reduction of bovine plasma cholesterol concentration by partial interruption of enterohepatic circulation of bile salts: a novel hypocholesterolemic model
Z Chen, TH Herdt, JS Liesman, NK Ames and RS Emery
Department of Animal Sciences, Michigan State University, East Lansing 48824, USA.
Interruption of enterohepatic circulation (EHC) of bile salts in several
species is known to cause a significant decrease in plasma concentrations
of low density lipoprotein (LDL) cholesterol, but to have little effect on
high density lipoprotein (HDL) cholesterol. The present study, for the
first time, demonstrates that partial interruption of EHC dramatically
reduces both plasma LDL and HDL cholesterol concentrations in cattle. Five
adult Holstein cows were surgically altered to allow controlled portions of
bile flow to be diverted from the body. The animals were fed a low-fat,
cholesterol- free diet. In two experiments, bile was diverted at 50% and
22% of total flow rates. By day 8 of diversion, both rates reduced mean
plasma cholesterol from baseline (85 mg/dl) to about 8 and 18 mg/dl,
respectively. Cholesterol was reduced in equal proportions in all
lipoprotein fractions. In addition, plasma concentrations of triglycerides
and phospholipids were also dramatically reduced. All of these plasma
lipids returned to baseline within 1 week after restoration of bile flow.
To determine the hepatic response to bile diversion, liver cholesterol
concentrations, cholesterol synthesis rates, and LDL receptor-binding
activities were determined in biopsy samples. In response to bile
diversion, hepatic cholesteryl esters were markedly depleted while hepatic
cholesterol synthesis rates were increased by more than 10-fold.
Nevertheless, because the basal cholesterol synthesis rate was so low, it
was estimated that the increase in synthesis would have supplied no more
than 5% of the sterols depleted during bile diversion (1.2 vs. 25
mmol/day). LDL receptor-binding activity was significantly elevated,
suggesting an increased uptake of plasma lipoprotein cholesterol by the
liver. These results suggest that the unique sensitivity of bovine plasma
cholesterol to enterohepatic circulation interruption might occur as a
result of the inherently low rate of hepatic cholesterol synthesis in
cattle. This hypocholesterolemic model might serve as an interesting tool
for the study of factors regulating plasma HDL cholesterol.
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