Improved metabolic control by depletion of Liver X Receptors in mice

Biochem Biophys Res Commun. 2006 Sep 15;348(1):176-82. doi: 10.1016/j.bbrc.2006.07.044. Epub 2006 Jul 18.

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 LXRalpha(-/-)beta(-/-) mice. Irrespective of diets, LXRalpha(-/-)beta(-/-) 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 LXRalpha(-/-)beta(-/-) mice and increased hepatic triglyceride content and mRNA levels of lipogenic genes in wild-type and LXRalpha(-/-)beta(-/-) mice, proportionally. In wild-type mice high carbohydrate diet was associated with induced expression of LXR (1.5-fold), despite unchanged SREBP-1c expression. LXRalpha(-/-)beta(-/-) mice responded to this diet by induction of SREBP-1c. Our study suggests that in LXRalpha(-/-)beta(-/-) mice, glucose utilization seems to be privileged possibly due to reduced circulating free fatty acid levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Carbohydrate Metabolism
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Diet
  • Gene Deletion
  • Insulin / metabolism
  • Lipid Metabolism
  • Liver X Receptors
  • Mice
  • Orphan Nuclear Receptors
  • Receptors, Cytoplasmic and Nuclear* / genetics
  • Receptors, Cytoplasmic and Nuclear* / metabolism

Substances

  • Blood Glucose
  • DNA-Binding Proteins
  • Insulin
  • Liver X Receptors
  • Nr1h3 protein, mouse
  • Orphan Nuclear Receptors
  • Receptors, Cytoplasmic and Nuclear