Lipoprotein synthesis is controlled by estrogens, but the exact mechanisms underpinning this regulation and the role of the hepatic estrogen receptor α (ERα) in cholesterol physiology are unclear. Utilizing a mouse model involving selective ablation of ERα in the liver, we demonstrate that hepatic ERα 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, ERα 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 α (LXRα) mediates the broad effects of ERα on the hepatic lipid metabolism.

An essential role for liver ERα in coupling hepatic metabolism to the reproductive cycle / S. Della Torre, N. Mitro, R. Fontana, M. Gomaraschi, E. Favari, C. Recordati, F. Lolli, F. Quagliarini, C. Meda, C. Ohlsson, M. Crestani, N.H. Uhlenhaut, L. Calabresi, A. Maggi. - In: CELL REPORTS. - ISSN 2211-1247. - 15:2(2016), pp. 360-371. [10.1016/j.celrep.2016.03.019]

An essential role for liver ERα in coupling hepatic metabolism to the reproductive cycle

S. Della Torre;N. Mitro;R. Fontana;M. Gomaraschi;C. Recordati;F. Lolli;C. Meda;M. Crestani;L. Calabresi;A. Maggi
2016

Abstract

Lipoprotein synthesis is controlled by estrogens, but the exact mechanisms underpinning this regulation and the role of the hepatic estrogen receptor α (ERα) in cholesterol physiology are unclear. Utilizing a mouse model involving selective ablation of ERα in the liver, we demonstrate that hepatic ERα 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, ERα 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 α (LXRα) mediates the broad effects of ERα on the hepatic lipid metabolism.
Settore BIO/14 - Farmacologia
A novel hypothesis on the development of metabolic syndrome in women
Role of the Liver Estrogen Receptor in female Energy Metabolism, Reproduction and Aging: What About Your Liver Sexual Functions?
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/398567
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