title: Silencing Mediator of Retinoid and Thyroid Hormone Receptors (SMRT) regulates glucocorticoid action in adipocytes.
abstract: Local modulation of glucocorticoid action in adipocytes regulates adiposity and systemic insulin sensitivity. However, the specific cofactors that mediate glucocorticoid receptor (GR) action in adipocytes remain unclear. Here we show that the silencing mediator of retinoid and thyroid hormone receptors (SMRT) is recruited to GR in adipocytes and regulates ligand-dependent GR function. Decreased SMRT expression in adipocytes in vivo increases expression of glucocorticoid-responsive genes. Moreover, adipocytes with decreased SMRT expression exhibit altered glucocorticoid regulation of lipolysis. We conclude that SMRT regulates the metabolic functions of GR in adipocytes in vivo. Modulation of GR-SMRT interactions in adipocytes represents a novel approach to control the local degree of glucocorticoid action and thus influence adipocyte metabolic function.
authors.affiliation: Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The University of Chicago, 900 E 57th Street, KCBD 8126, Chicago, IL 60637, USA.
authors.forename: Margo P
authors.initials: MP
authors.lastname: Emont
authors.affiliation: Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The University of Chicago, 900 E 57th Street, KCBD 8126, Chicago, IL 60637, USA.
authors.forename: Stelios
authors.initials: S
authors.lastname: Mantis
authors.affiliation: Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The University of Chicago, 900 E 57th Street, KCBD 8126, Chicago, IL 60637, USA.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Kahn
authors.affiliation: Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The University of Chicago, 900 E 57th Street, KCBD 8126, Chicago, IL 60637, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Landeche
authors.affiliation: Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The University of Chicago, 900 E 57th Street, KCBD 8126, Chicago, IL 60637, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Han
authors.affiliation: Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The University of Chicago, 900 E 57th Street, KCBD 8126, Chicago, IL 60637, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sargis
authors.affiliation: Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The University of Chicago, 900 E 57th Street, KCBD 8126, Chicago, IL 60637, USA. Electronic address: roncohen@medicine.bsd.uchicago.edu.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Cohen
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004822:Epididymis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008066:Lipolysis / Q000187:drug effects / Q000235:genetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056985:Nuclear Receptor Co-Repressor 2 / Q000235:genetics* / Q000378:metabolism; D010711:Phosphatidate Phosphatase / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D021381:Protein Transport; D020239:Receptor Cross-Talk; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C498608:Dsip1 protein, mouse; C539131:Ncor2 protein, mouse; D009687:Nuclear Proteins; D056985:Nuclear Receptor Co-Repressor 2; D011965:Receptors, Glucocorticoid; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; D003907:Dexamethasone; D008156:Luciferases; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase
keywords: Adipocyte; Corepressor; Glucocorticoid; Nuclear receptor