An Essential Role for Liver ERα in Coupling Hepatic Metabolism to the Reproductive Cycle

被引：105

作者：

Della Torre, Sara ^{[1
,2
]}

Mitro, Nico ^{[2
]}

Fontana, Roberta ^{[2
,3
]}

Gomaraschi, Monica ^{[2
]}

Favari, Elda ^{[4
]}

Recordati, Camilla ^{[5
]}

Lolli, Federica ^{[1
,2
]}

Quagliarini, Fabiana ^{[6
,7
]}

Meda, Clara ^{[1
,2
]}

Ohlsson, Claes ^{[8
,9
]}

Crestani, Maurizio ^{[2
]}

Uhlenhaut, Nina Henriette ^{[6
,7
]}

Calabresi, Laura ^{[2
]}

Maggi, Adriana ^{[1
,2
]}

机构：

[1] Univ Milan, Ctr Excellence Neurodegenerat Dis, I-20133 Milan, Italy

[2] Univ Milan, Dept Pharmacol & Biomol Sci, I-20133 Milan, Italy

[3] Italian Inst Technol, Dept Drug Discovery & Dev, I-16163 Genoa, Italy

[4] Univ Parma, Dept Pharm, I-43121 Parma, Italy

[5] Fdn Filarete, Mouse & Anim Pathol Lab, I-20139 Milan, Italy

[6] Helmholtz Zentrum Muenchen, HDC, D-85764 Munich, Germany

[7] Helmholtz Zentrum Muenchen, German Ctr Diabet Res DZD, D-85764 Munich, Germany

[8] Univ Gothenburg, Ctr Bone & Arthrit Res, Sahlgrenska Acad, S-40530 Gothenburg, Sweden

[9] Univ Gothenburg, Dept Internal Med & Clin Nutr, Sahlgrenska Acad, Inst Med, S-40530 Gothenburg, Sweden

来源：

CELL REPORTS | 2016年 / 15卷 / 02期

基金：

欧洲研究理事会;

关键词：

CHOLESTEROL EFFLUX CAPACITY; FATTY LIVER; RECEPTOR-ALPHA; GENE-EXPRESSION; X-RECEPTOR; ESTROGEN; DISEASE; WOMEN;

D O I：

10.1016/j.celrep.2016.03.019

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Lipoprotein synthesis is controlled by estrogens, but the exact mechanisms underpinning this regulation and the role of the hepatic estrogen receptor alpha (ER alpha) in cholesterol physiology are unclear. Utilizing a mouse model involving selective ablation of ER alpha in the liver, we demonstrate that hepatic ER alpha couples lipid metabolism to the reproductive cycle. We show that this receptor regulates the synthesis of cholesterol transport proteins, enzymes for lipoprotein remodeling, and receptors for cholesterol uptake. Additionally, ER alpha is indispensable during proestrus for the generation of high-density lipoproteins efficient in eliciting cholesterol efflux from macrophages. We propose that a specific interaction with liver X receptor alpha (LXR alpha) mediates the broad effects of ER alpha on the hepatic lipid metabolism.

引用

页码：360 / 371

页数：12

共 32 条

[1] Hepatic VLDL-TG Production and MTP Gene Expression are Decreased in Ovariectomized Rats: Effects of Exercise Training [J].