The
cancer-preventing
selective estrogen receptor modulator (
SERM)
acolbifene (ACOL) exerts a potent and pure antiestrogenic action in the mammary gland and uterus, yet it displays beneficial,
estrogen-like actions on energy and lipid metabolism in rodents. The compound reduces food intake and strongly decreases cholesterolemia in rats fed a
cholesterol-free diet. This study was designed to establish whether the
anorectic effect of ACOL is involved in its
cholesterol-lowering action, and whether the compound retains its ability to lower
cholesterol concentrations in rats with diet-induced
hypercholesterolemia. Female rats were fed a purified diet devoid of
cholesterol (reference diet) or containing 2%
cholesterol (C-diet); they were either not treated or treated daily with ACOL or not treated and pair-fed to the ACOL-treated rats. The C-diet did not affect food intake or weight and fat gains. ACOL reduced food intake (16%) and
weight gain (45%, mainly fat) similarly in both dietary cohorts. ACOL, but not pair feeding, reduced cholesterolemia by 33% in rats fed the reference diet. As expected, the C-diet raised serum total
cholesterol almost 3-fold and this increase was largely prevented by ACOL but not by pair feeding.
Cholesterol was reduced by ACOL, mainly in the HDL fraction, in rats fed the reference diet, but only in the non-HDL fraction in those fed the C-diet. In livers of rats fed the reference diet, ACOL, but not pair feeding, increased
protein abundance of the
scavenger receptor, class B, type 1, and the
LDL receptor, thought to be involved in ACOL-mediated
cholesterol lowering. These findings demonstrate that the potent hypocholesterolemic action of ACOL is independent of the concomitant reduction in food intake and fat accretion, and that such action occurs in rats with overt diet-induced
hypercholesterolemia.