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Estetrol prevents western diet-induced obesity and atheroma independently of hepatic estrogen receptor (ER)α
- Source :
- AJP-Endocrinology and Metabolism, AJP-Endocrinology and Metabolism, 2021, 320 (1), pp.E19-E29. ⟨10.1152/ajpendo.00211.2020⟩, AJP-Endocrinology and Metabolism, American Physiological Society, 2021, 320 (1), pp.E19-E29. ⟨10.1152/ajpendo.00211.2020⟩
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
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 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.
- Subjects :
- 0301 basic medicine
Physiology
Endocrinology, Diabetes and Metabolism
[SDV]Life Sciences [q-bio]
Estrogen receptor
menopause
Mice
chemistry.chemical_compound
0302 clinical medicine
Mice, Knockout
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Estetrol
Fatty liver
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Lipids
Plaque, Atherosclerotic
3. Good health
Menopause
[SDV] Life Sciences [q-bio]
Adipose Tissue
Liver
Female
estrogen receptor
medicine.medical_specialty
medicine.drug_class
Ovariectomy
030209 endocrinology & metabolism
metabolic syndrome
03 medical and health sciences
Physiology (medical)
Internal medicine
medicine
Animals
Obesity
fatty liver
business.industry
Cholesterol
Estrogen Receptor alpha
Glucose Tolerance Test
medicine.disease
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
Receptors, LDL
chemistry
Diet, Western
Estrogen
Hepatocytes
Steatosis
Metabolic syndrome
atherosclerosis
business
Subjects
Details
- Language :
- English
- ISSN :
- 01931849 and 15221555
- Database :
- OpenAIRE
- Journal :
- AJP-Endocrinology and Metabolism, AJP-Endocrinology and Metabolism, 2021, 320 (1), pp.E19-E29. ⟨10.1152/ajpendo.00211.2020⟩, AJP-Endocrinology and Metabolism, American Physiological Society, 2021, 320 (1), pp.E19-E29. ⟨10.1152/ajpendo.00211.2020⟩
- Accession number :
- edsair.doi.dedup.....cd6ae05ba8b11ae573eeffb1e1b05905