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

Publication date: Available online 31 March 2016
Source:Cell Reports
Author(s): Sara Della Torre, Nico Mitro, Roberta Fontana, Monica Gomaraschi, Elda Favari, Camilla Recordati, Federica Lolli, Fabiana Quagliarini, Clara Meda, Claes Ohlsson, Maurizio Crestani, Nina Henriette Uhlenhaut, Laura Calabresi, Adriana Maggi
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.

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Teaser

Della Torre et al. show that ERα activity in the mouse female liver is essential for balanced lipid and cholesterol metabolism. Lack of liver ERα activation in the case of ovarian failure leads to metabolic dysfunction that may be linked to post-menopausal disease.


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