Improved metabolic control by depletion of Liver X Receptors in mice

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.