title: An Essential Role for Liver ERα in Coupling Hepatic Metabolism to the Reproductive Cycle.
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.
authors.affiliation: Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Della Torre
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy.
authors.forename: Nico
authors.initials: N
authors.lastname: Mitro
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy; Department of Drug Discovery and Development, Italian Institute of Technology, 16163 Genova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Fontana
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Gomaraschi
authors.affiliation: Department of Pharmacy, University of Parma, 43121 Parma, Italy.
authors.forename: Elda
authors.initials: E
authors.lastname: Favari
authors.affiliation: Mouse and Animal Pathology Laboratory, Fondazione Filarete, 20139 Milan, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Recordati
authors.affiliation: Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Lolli
authors.affiliation: Helmholtz Diabetes Center (HDC) and German Center for Diabetes Research (DZD), Helmholtz Zentrum Muenchen, 85764 Munich-Neuherberg, Germany.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Quagliarini
authors.affiliation: Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Meda
authors.affiliation: Centre for Bone and Arthritis Research and Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Crestani
authors.affiliation: Helmholtz Diabetes Center (HDC) and German Center for Diabetes Research (DZD), Helmholtz Zentrum Muenchen, 85764 Munich-Neuherberg, Germany.
authors.forename: Nina Henriette
authors.initials: NH
authors.lastname: Uhlenhaut
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Calabresi
authors.affiliation: Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy. Electronic address: adriana.maggi@unimi.it.
authors.forename: Adriana
authors.initials: A
authors.lastname: Maggi
mesh_terms: D050154:Adiposity; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D030762:Estrous Cycle; D005260:Female; D017353:Gene Deletion; D008074:Lipoproteins / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D000071518:Liver X Receptors / Q000378:metabolism; D018345:Mice, Knockout; D047493:PPAR alpha / Q000378:metabolism; D011485:Protein Binding; D012098:Reproduction; D014158:Transcription, Genetic
chemical_list: D047628:Estrogen Receptor alpha; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D000071518:Liver X Receptors; D047493:PPAR alpha; D003094:Collagen; D002784:Cholesterol