title: Once and for all, LXRα and LXRβ are gatekeepers of the endocrine system.
abstract: Liver X receptors (LXRs) α and β are nuclear receptors whose transcriptional activity is regulated by oxysterols, the oxidized forms of cholesterol. Described in the late 1990s as lipid sensors, both LXRs regulate cholesterol and fatty acid homeostasis. Over the years, deep phenotypic analyses of mouse models deficient for LXRα and/or LXRβ have pointed out various other physiological functions including glucose homeostasis, immunology, and neuroprotection. This review enlightens the "endocrine" functions of LXRs; they deeply impact plasma glucose directly and by modulating insulin signaling, renin-angiotensin-aldosterone axis, thyroid and pituitary hormone levels, and bone homeostasis. Besides, LXR signaling is also involved in adrenal physiology, steroid synthesis, and male and female reproduction. Hence, LXRs are definitely involved in the endocrine system and could thus be considered as endocrine receptors, even though oxysterols do not fully correspond to the definition of hormones. Finally, because they are ligand-regulated transcription factors, LXRs are potential pharmacological targets with promising beneficial metabolic effects.
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, Génétique Reproduction et Développement, 28, place Henri Dunant, BP38, F63001 Clermont-Ferrand, France; CNRS UMR 6293, GReD, 10 Avenue Blaise Pascal, Campus Universitaire des Cézeaux, CS60026, F-63178 Aubiere, France; INSERM UMR 1103, GReD, 10 Avenue Blaise Pascal, Campus Universitaire des Cézeaux, CS60026, F-63178 Aubiere, France; Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009 Clermont-Ferrand, France; Service d'Endocrinologie, Diabétologie et Maladies Métaboliques, Hôpital Gabriel Montpied, 58 Boulevard Montalembert, F-63003 Clermont-Ferrand, France.
authors.forename: Salwan
authors.initials: S
authors.lastname: Maqdasy
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, Génétique Reproduction et Développement, 28, place Henri Dunant, BP38, F63001 Clermont-Ferrand, France; CNRS UMR 6293, GReD, 10 Avenue Blaise Pascal, Campus Universitaire des Cézeaux, CS60026, F-63178 Aubiere, France; INSERM UMR 1103, GReD, 10 Avenue Blaise Pascal, Campus Universitaire des Cézeaux, CS60026, F-63178 Aubiere, France; Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009 Clermont-Ferrand, France.
authors.forename: Amalia
authors.initials: A
authors.lastname: Trousson
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, Génétique Reproduction et Développement, 28, place Henri Dunant, BP38, F63001 Clermont-Ferrand, France; CNRS UMR 6293, GReD, 10 Avenue Blaise Pascal, Campus Universitaire des Cézeaux, CS60026, F-63178 Aubiere, France; INSERM UMR 1103, GReD, 10 Avenue Blaise Pascal, Campus Universitaire des Cézeaux, CS60026, F-63178 Aubiere, France; Service d'Endocrinologie, Diabétologie et Maladies Métaboliques, Hôpital Gabriel Montpied, 58 Boulevard Montalembert, F-63003 Clermont-Ferrand, France.
authors.forename: Igor
authors.initials: I
authors.lastname: Tauveron
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, Génétique Reproduction et Développement, 28, place Henri Dunant, BP38, F63001 Clermont-Ferrand, France; CNRS UMR 6293, GReD, 10 Avenue Blaise Pascal, Campus Universitaire des Cézeaux, CS60026, F-63178 Aubiere, France; INSERM UMR 1103, GReD, 10 Avenue Blaise Pascal, Campus Universitaire des Cézeaux, CS60026, F-63178 Aubiere, France; Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009 Clermont-Ferrand, France.
authors.forename: David H
authors.initials: DH
authors.lastname: Volle
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, Génétique Reproduction et Développement, 28, place Henri Dunant, BP38, F63001 Clermont-Ferrand, France; CNRS UMR 6293, GReD, 10 Avenue Blaise Pascal, Campus Universitaire des Cézeaux, CS60026, F-63178 Aubiere, France; INSERM UMR 1103, GReD, 10 Avenue Blaise Pascal, Campus Universitaire des Cézeaux, CS60026, F-63178 Aubiere, France; Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009 Clermont-Ferrand, France. Electronic address: silvere.baron@univ-bpclermont.fr.
authors.forename: Silvère
authors.initials: S
authors.lastname: Baron
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, Génétique Reproduction et Développement, 28, place Henri Dunant, BP38, F63001 Clermont-Ferrand, France; CNRS UMR 6293, GReD, 10 Avenue Blaise Pascal, Campus Universitaire des Cézeaux, CS60026, F-63178 Aubiere, France; INSERM UMR 1103, GReD, 10 Avenue Blaise Pascal, Campus Universitaire des Cézeaux, CS60026, F-63178 Aubiere, France; Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009 Clermont-Ferrand, France. Electronic address: j-marc.lobaccaro@univ-bpclermont.fr.
authors.forename: Jean-Marc A
authors.initials: JM
authors.lastname: Lobaccaro
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004703:Endocrine System / Q000502:physiology*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D000071518:Liver X Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D012098:Reproduction; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D006728:Hormones; D007328:Insulin; D000071518:Liver X Receptors; D014157:Transcription Factors; D002784:Cholesterol; D005947:Glucose
keywords: Cholesterol; Endocrinology; Liver X receptors; Pharmacology; Reproduction