Article (Scientific journals)
Estetrol prevents western diet-induced obesity and atheroma independently of hepatic estrogen receptor (ER)α
Buscato, Mélissa; Davezac, Morgane; Zahreddine, Rana et al.
2021In American Journal of Physiology - Endocrinology and Metabolism, 320
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Keywords :
estrogen receptor; menopause; fatty liver; atherosclerosis; metabolic syndrome
Abstract :
[en] 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 with 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 estrogen receptor (ER) α in the preventive effect of E4 against obesity and associated disorders such as atherosclerosis and steatosis, mice harboring a hepatocyte-specific ERα deletion (LERKO) were crossed with LDLR-/- mice. Our results demonstrated that, whereas liver ERα is dispensable for the E4 beneficial actions on obesity and atheroma, it is necessary to prevent steatosis in mice. Overall, these findings suggest that E4 could prevent metabolic, hepatic, and vascular disorders occurring at menopause, extending the potential medical interest of this natural estrogen as a new hormonal treatment.NEW & NOTEWORTHY Estetrol prevents obesity, steatosis, and atherosclerosis in mice fed a Western diet. Hepatic ERα is necessary for the prevention of steatosis, but not of obesity and atherosclerosis.
Research center :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Buscato, Mélissa
Davezac, Morgane
Zahreddine, Rana
Adlanmerini, Marine
Métivier, Raphaël
Fillet, Marianne ;  Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
COBRAIVILLE, Gaël ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie
Moro, Cedric
Foidart, Jean-Michel 
Lenfant, Françoise
Gourdy, Pierre
Amal, Jean-François
Fontaine, Coralie
More authors (3 more) Less
Language :
English
Title :
Estetrol prevents western diet-induced obesity and atheroma independently of hepatic estrogen receptor (ER)α
Publication date :
2021
Journal title :
American Journal of Physiology - Endocrinology and Metabolism
ISSN :
0193-1849
eISSN :
1522-1555
Publisher :
American Physiological Society, United States - Maryland
Volume :
320
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 17 April 2021

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