Improved metabolic control by depletion of Liver X Receptors in mice
Copyright policy )Improved metabolic control by depletion of Liver X Receptors in mice
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.
- Karolinska Institute Sweden
- Karolinska University Hospital Sweden
- Martin Luther University Halle-Wittenberg Germany
Blood Glucose, Receptors, Cytoplasmic and Nuclear, Lipid Metabolism, Orphan Nuclear Receptors, Diet, DNA-Binding Proteins, Mice, Animals, Carbohydrate Metabolism, Insulin, Gene Deletion, Liver X Receptors
Blood Glucose, Receptors, Cytoplasmic and Nuclear, Lipid Metabolism, Orphan Nuclear Receptors, Diet, DNA-Binding Proteins, Mice, Animals, Carbohydrate Metabolism, Insulin, Gene Deletion, Liver X Receptors
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