Improved metabolic control by depletion of Liver X Receptors in mice

Gertrud U. Schuster, Lisen Johansson, Silke Kietz, Thomas M. Stulnig, Paolo Parini, Jan Åke Gustafsson

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Liver X Receptors (LXRs) coordinate the regulation of lipid and carbohydrate metabolism and insulin signaling. LXR-ligands lower plasma glucose in hyperglycemic rodents and have consequently been proposed as anti-diabetic agents. We investigated the metabolic effects induced by high carbohydrate diet in LXRα-/-β-/- mice. Irrespective of diets, LXRα-/-β-/- mice had reduced fatty acid, insulin, and C-peptide plasma levels than wild-type controls, suggesting a lower insulin production. High carbohydrate diet decreased the plasma glucose levels and the homeostasis model assessment (HOMA)-index in LXRα-/-β-/- mice and increased hepatic triglyceride content and mRNA levels of lipogenic genes in wild-type and LXRα-/-β-/- mice, proportionally. In wild-type mice high carbohydrate diet was associated with induced expression of LXR (1.5-fold), despite unchanged SREBP-1c expression. LXRα-/-β-/- mice responded to this diet by induction of SREBP-1c. Our study suggests that in LXRα-/-β-/- mice, glucose utilization seems to be privileged possibly due to reduced circulating free fatty acid levels.

Original languageEnglish (US)
Pages (from-to)176-182
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume348
Issue number1
DOIs
StatePublished - Sep 15 2006

Keywords

  • Insulin receptor substrate 2
  • Liver X Receptor
  • Serum glucose levels

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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