Novel oestrogen receptor β-selective ligand reduces obesity and depressive-like behaviour in ovariectomized mice

• Main Authors: Daimei Sasayama, Nobuhiro Sugiyama, Shigeru Yonekubo, Akiko Pawlak, Hiroyasu Murasawa, Mie Nakamura, Morimichi Hayashi, Takashi Ogawa, Makoto Moro, Shinsuke Washizuka, Naoji Amano, Kazuhiro Hongo, Hideki Ohnota
• Format: Article
• Language: English
• Published: Nature Publishing Group 2017-07-01
• Series: Scientific Reports
• Online Access: https://doi.org/10.1038/s41598-017-04946-5

Abstract Hormonal changes due to menopause can cause various health problems including weight gain and depressive symptoms. Multiple lines of evidence indicate that oestrogen receptors (ERs) play a major role in postmenopausal obesity and depression. However, little is known regarding the ER subtype-specific effects on obesity and depressive symptoms. To delineate potential effects of ERβ activation in postmenopausal women, we investigated the effects of a novel oestrogen receptor β-selective ligand (C-1) in ovariectomized mice. Uterine weight, depressive behaviour, and weight gain were examined in sham-operated control mice and ovariectomized mice administered placebo, C-1, or 17β-oestradiol (E2). Administration of C-1 or E2 reduced body weight gain and depressive-like behaviour in ovariectomized mice, as assessed by the forced swim test. In addition, administration of E2 to ovariectomized mice increased uterine weight, but administration of C-1 did not result in a significant increase in uterine weight. These results suggest that the selective activation of ERβ in ovariectomized mice may have protective effects against obesity and depressive-like behaviour without causing an increase in uterine weight. The present findings raise the possibility of the application of ERβ-ligands such as C-1 as a novel treatment for obesity and depression in postmenopausal women.