Chronic estrogen replacement in ovariectomized rats attenuates food intake and enhances c-Fos expression in the suprachiasmatic nucleus (SCN), specifically during the light phase.-equol, a metabolite of daidzein, has a strong affinity for estrogen receptor (ER)-β and exerts estrogenic activity. The purpose of the present study was to elucidate whether-equol exerts an estrogen-like anorectic effect by modifying the regulation of the circadian feeding rhythm in ovariectomized rats. Ovariectomized female Wistar rats were divided into an estradiol (E2)-replaced group and cholesterol (vehicle; Veh)-treated group. These animals were fed either a standard diet or an-equol-containing diet for 13 days. Then, the brain, uterus, and pituitary gland were collected along with blood samples. In the rats fed the standard diet, E2 replacement attenuated food intake ( < 0.001) and enhanced c-Fos expression in the SCN ( < 0.01) during the light phase. Dietary-equol supplementation reduced food intake ( < 0.01) and increased c-Fos expression in the SCN ( < 0.01) in the Veh-treated rats but not in the E2-replaced rats during the light phase. Dietary-equol did not alter ER-α expression in the medial preoptic area or the arcuate nucleus, nor did dietary S-equol affect pituitary gland weight or endometrial epithelial layer thickness. By contrast, E2 replacement not only markedly decreased ER-α expression in these brain areas ( < 0.001) but also increased both the pituitary gland weight ( < 0.001) and the endometrial epithelial layer thickness ( < 0.001). Thus, dietary-equol acts as an anorectic by modifying the diurnal feeding pattern in a manner similar to E2 in ovariectomized rats; however, the mechanism of action is not likely to be mediated by ER-α. The data suggest a possibility that dietary-equol could be an alternative to hormone replacement therapy for the prevention of hyperphagia and obesity with a lower risk of adverse effects induced by ER-α stimulation. S S S P P S P P S P P P S S
