Journal of Lipid Research, Vol 28, 1281-1295, Copyright © 1987 by Lipid Research, Inc.
Modulation of low density lipoprotein receptor activity by bile acids: differential effects of chenodeoxycholic and ursodeoxycholic acids in the hamster
M Malavolti, H Fromm, S Ceryak and IM Roberts
Department of Medicine, George Washington University Medical Center, Washington, DC 20037.
Hamsters were fed chenodeoxycholic acid (CDC), ursodeoxycholic acid, (UDC),
or no bile acid. [14C]Sucrose-labeled hamster low density lipoprotein (LDL)
and methylated human LDL were infused intravenously to study LDL
receptor-dependent and LDL receptor-independent organ uptake, respectively,
of LDL. Biliary CDC increased during both CDC and UDC treatment. The UDC
enrichment of bile after UDC feeding was relatively small. Bile acid
synthesis was suppressed after both bile acid treatments. Under the
condition of an acute bile fistula, the hamster LDL uptake increased in the
liver, heart, and adrenals in the CDC-treated animals. During an intact
enterohepatic circulation, the hepatic uptake of hamster LDL, which
accounted for a major portion of the total uptake, was increased after UDC
treatment. The hamster LDL uptake in the colon, which represented only a
small fraction of the total uptake, increased after CDC treatment. When
hamster LDL was infused at increasing concentrations, its uptake was
significantly higher in the UDC-treated than in the control and CDC-treated
animals. The methylated human LDL uptake showed no significant changes in
the different treatment groups under either experimental condition. The
study shows significantly different effects of CDC and UDC on LDL receptor
activity. Since these differences are expressed in spite of a similar
suppression of bile acid synthesis, UDC may directly influence LDL receptor
activity.
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