Silencing Mediator of Retinoid and Thyroid Hormone Receptors (SMRT) regulates glucocorticoid action in adipocytes

Mol Cell Endocrinol. 2015 May 15;407:52-6. doi: 10.1016/j.mce.2015.03.002. Epub 2015 Mar 9.

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.

Keywords: Adipocyte; Corepressor; Glucocorticoid; Nuclear receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipose Tissue / cytology
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Dexamethasone / pharmacology*
  • Epididymis / cytology
  • Epididymis / drug effects
  • Epididymis / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Genes, Reporter
  • Lipolysis / drug effects
  • Lipolysis / genetics
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • Mice
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Receptor Co-Repressor 2 / genetics*
  • Nuclear Receptor Co-Repressor 2 / metabolism
  • Phosphatidate Phosphatase / genetics
  • Phosphatidate Phosphatase / metabolism
  • Primary Cell Culture
  • Protein Transport
  • Receptor Cross-Talk
  • Receptors, Glucocorticoid / genetics*
  • Receptors, Glucocorticoid / metabolism
  • Receptors, Thyroid Hormone / genetics*
  • Receptors, Thyroid Hormone / metabolism
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Dsip1 protein, mouse
  • Ncor2 protein, mouse
  • Nuclear Proteins
  • Nuclear Receptor Co-Repressor 2
  • Receptors, Glucocorticoid
  • Receptors, Thyroid Hormone
  • Transcription Factors
  • Dexamethasone
  • Luciferases
  • Lpin1 protein, mouse
  • Phosphatidate Phosphatase