Effect of dietary cholesterol and taurocholate on cholesterol 7 alpha-hydroxylase and hepatic LDL receptors in inbred mice.
Compared to BALB/c mice, inbred C57BL/6 mice are more susceptible to developing fatty streak atherosclerotic lesions when fed a cholesterol-rich diet containing taurocholate. We examined the metabolic basis for the taurocholate requirement. In contrast to widely accepted assumptions, taurocholate did not increase cholesterol absorption in either strain of mouse. However, in susceptible C57BL/6 mice, taurocholate was required to increase plasma concentrations of apoB. In both strains, the cholesterol-rich diet increased both the activity and mRNA for 7 alpha-hydroxylase, a compensatory response to maintain cholesterol homeostasis. In both strains, adding taurocholate to the diet suppressed both the activity and mRNA for 7 alpha-hydroxylase, thus blocking this important compensatory response. The cholesterol-rich diet (without taurocholate) significantly increased hepatic cholesterol content in both strains of mice, but repressed low density lipoprotein (LDL) receptor mRNA only in BALB/c mice (not in C57BL/6 mice). However, adding taurocholate to the cholesterol-rich diet did decrease LDL receptor mRNA in C57BL/6 mice. In C57BL/6, but not in BALB/c mice, there was a linear parallel relationship between 7 alpha-hydroxylase mRNA and LDL receptor mRNA. These data show the existence of strain-specific differences in the effects of dietary cholesterol and taurocholate on 7 alpha-hydroxylase and LDL receptor expression. The combined data suggest that genetic factors determine how the expression of hepatic LDL receptors responds to dietary cholesterol and taurocholate.
Dueland
S
S
Atherosclerosis Research Center, University of Colorado Health Sciences Center, Denver 80262.
Drisko
J
J
Graf
L
L
Machleder
D
D
Lusis
A J
AJ
Davis
R A
RA
D000818:Animals; D001055:Apolipoproteins B / Q000097:blood; D001646:Bile / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000493:pharmacokinetics / Q000494:pharmacology*; D004032:Diet; D005260:Female; D007408:Intestinal Absorption / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011973:Receptors, LDL / Q000378:metabolism*; D013045:Species Specificity; D013656:Taurocholic Acid / Q000494:pharmacology*
D001055:Apolipoproteins B; D002791:Cholesterol, Dietary; D011973:Receptors, LDL; D013656:Taurocholic Acid; D002790:Cholesterol 7-alpha-Hydroxylase