Expression of the Insulin-responsive Glucose Transporter GLUT4 in Adipocytes Is Dependent on Liver X Receptor α

Knut Tomas Dalen, Stine Marie Ulven, Krister Bamberg, Jan Åke Gustafsson, Hilde I. Nebb

Research output: Contribution to journalArticle

137 Scopus citations

Abstract

The insulin-responsive glucose transporter GLUT4 plays a crucial role in insulin-mediated facilitated glucose uptake into adipose tissue and muscle, and impaired expression of GLUT4 has been linked to obesity and diabetes. In this study, we demonstrate that liver X receptors (LXRs) regulate the expression of GLUT4 through direct interaction with a conserved LXR response element in the GLUT4 promoter. The expression of GLUT4 in WAT is induced by a potent LXR agonist in wild type, LXRα-/-, and LXRβ-/- mice but not in LXRα-/-β-/- mice, demonstrating that both LXRs are able to mediate ligand activated transcription of the GLUT4 gene. However, basal and insulin stimulated expression of GLUT4 in epididymal WAT is reduced only in mice carrying ablation of the LXRα isoform. The expression of GLUT4 is furthermore correlated to the induction of LXRα during mouse and human adipocyte differentiation. LXRβ is thus apparently not able to rescue basal expression of GLUT4 in the absence of LXRα. We have previously demonstrated that LXRα is down-regulated in animal models of obesity and diabetes, thus revealing a striking correlation between GLUT4 and LXRα expression in insulin-resistant conditions. This suggests that the LXRα isoform has a unique role in adipose expression of GLUT4 and suggests that alteration of adipose tissue expression of LXRΑ might be a novel tool to normalize the expression of a gene that is dysregulated in diabetic and insulin-resistant conditions.

Original languageEnglish (US)
Pages (from-to)48283-48291
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number48
DOIs
StatePublished - Nov 28 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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