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 d eveloping 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 assumpti ons, taurocholate did not increase cholesterol absorption in either st rain of mouse. However, in susceptible C57BL/6 mice, taurocholate was required to increase plasma concentrations of apoB. In both strains, t he cholesterol-rich diet increased both the activity and mRNA for 7alp ha-hydroxylase, a compensatory response to maintain cholesterol homeos tasis. In both strains, adding taurocholate to the diet suppressed bot h the activity and mRNA for 7alpha-hydroxylase, thus blocking this imp ortant compensatory response. The cholesterol-rich diet (without tauro cholate) significantly increased hepatic cholesterol content in both s trains of mice, but repressed low density lipoprotein (LDL) receptor m RNA only in BALB/c mice (not in C57BL/6 mice). However, adding tauroch olate to the cholesterol-rich diet did decrease LDL receptor mRNA in C 57BL/6 mice. In C57BL/6, but not in BALB/c mice, there was a linear pa rallel relationship between 7alpha-hydroxylase mRNA and LDL receptor m RNA. These data show the existence of strain-specific differences in t he effects of dietary cholesterol and taurocholate on 7alpha-hydroxyla se and LDL receptor expression. The combined data suggest that genetic factors determine how the expression of hepatic LDL receptors respond s to dietary cholesterol and taurocholate.