Hypocholesterolemic action of the selective estrogen receptor modulator acolbifene in intact and ovariectomized rats with diet-induced hypercholesterolemia

Metabolism: Clinical and Experimental
Christian LemieuxY Deshaies

Abstract

Acolbifene (ACOL) is a fourth-generation selective estrogen receptor modulator (SERM) that has strong and pure antiestrogenic properties toward estrogen-sensitive cancers, but improves energy and lipid metabolism in an estrogen-like fashion in rodent models. The aim of this study was to determine the potency of ACOL to reduce cholesterolemia in a dietary model of hypercholesterolemia and to establish its mechanisms of action. Intact and ovariectomized (OVX) female rats were treated for 3 weeks with ACOL, and serum cholesterol and liver determinants of cholesterol metabolism were assessed. Acolbifene prevented both diet- and ovariectomy-induced weight gain and completely prevented diet-induced hypercholesterolemia. Relative to a reference chow diet, the high-cholesterol diet decreased the high-density lipoprotein (HDL) cholesterol fraction, which remained unaffected by ACOL, indicating that in hypercholesterolemic conditions, ACOL modulated only the non-HDL fraction. No impact of ACOL on determinants of liver cholesterol synthesis was observed. In contrast, ACOL increased hepatic low-density lipoprotein receptor protein in both intact and OVX rats, which was negatively correlated with serum total and non-HDL cholesterol (r=-0.59...Continue Reading

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