Estrogen receptor alpha-mediated adiposity-lowering and hypocholesterolemic actions of the selective estrogen receptor modulator acolbifene.
OBJECTIVE
The selective estrogen receptor (ER) modulator (SERM) acolbifene (ACOL), a potent and pure antiestrogen in the mammary gland and uterus, exerts beneficial pro-estrogenic actions on energy balance, insulin sensitivity and lipid metabolism. ACOL binds ERs alpha and beta, both of which have been involved in the metabolic actions of estrogen. This study aimed at determining the identity of the ER involved in the beneficial metabolic actions of ACOL.


METHODS
ACOL was administered for 4 weeks to male and female wild-type and ERalpha knockout (KO) mice, and indices of energy balance as well as plasma and liver lipid concentrations were determined.


RESULTS
ERalpha KO mice were heavier, gained more fat mass and had larger adipose depots than their wild-type counterparts. In both genders, ACOL decreased fat gain (50%) and white adipose tissue mass in male and female wild-type, but not in ERalpha KO mice. ACOL reduced plasma cholesterol in female wild-type mice (-27%), whereas the compound remained ineffective in their ERalpha KO counterparts. Plasma triglycerides were unaffected by ACOL. Finally, ACOL decreased liver cholesterol and triglyceride concentrations only in wild-type female animals.


CONCLUSIONS
The beneficial metabolic actions of the SERM ACOL on adiposity and on plasma and liver lipids are entirely due to its interaction with the ERalpha.
Lemieux
C
C
Department of Anatomy and Physiology, Faculty of Medicine, Laval Hospital Research Center, Laval University, Quebec City, Quebec, Canada.
Phaneuf
D
D
Labrie
F
F
Giguère
V
V
Richard
D
D
Deshaies
Y
Y
D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D002784:Cholesterol / Q000097:blood*; D047628:Estrogen Receptor alpha / Q000187:drug effects*; D005260:Female; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000494:pharmacology*; D011897:Random Allocation; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood*
D047628:Estrogen Receptor alpha; D010880:Piperidines; D020845:Selective Estrogen Receptor Modulators; D014280:Triglycerides; C012121:ritetronium; D002784:Cholesterol