Estetrol prevents western diet-induced obesity and atheroma independently of hepatic estrogen receptor (ER) α.

Estetrol prevents western diet-induced obesity and atheroma independently of hepatic estrogen receptor (ER)α. Am J Physiol Endocrinol Metab. 2020 Nov 02;: Authors: Buscato M, Davezac M, Zahreddine R, Adlanmerini M, Metivier R, Fillet M, Cobraiville G, Moro C, Foidart JM, Lenfant F, Gourdy P, Arnal JF, Fontaine C Abstract Estetrol (E4), a natural estrogen synthesized by the human fetal liver, is currently evaluated in phase III clinical studies as a new menopause hormone therapy. Indeed, E4 significantly improves vasomotor and genito-urinary menopausal symptoms and prevents bone demineralization. Compared to other estrogens, E4 was found to have limited effects on coagulation factors in the liver of women allowing to expect less thrombotic events. To fully delineate its clinical potential, the aim of this study was to assess the effect of E4 on metabolic disorders. Here, we studied the pathophysiological consequences of a western diet (42% kcal fat, 0.2% cholesterol) in ovariectomized female mice under chronic E4 treatment. We showed that E4 reduces body weight gain and improves glucose tolerance in both C57Bl/6 and LDLR-/- mice. To evaluate the role of hepatic ERα in the preventive effect of E4 against obesity and associated disorders such as atherosclerosis and steatosis, mice harbouring a hepatocyte-specific ERα deletion (LERKO) were crossed with LDLR-/- mice. Our results demonstrated that, whereas liver ERα is dispensable for ...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research