Improved metabolic control by depletion of Liver X Receptors in mice

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• 作者：Gertrud U. Schuster ; Lisen Johansson ; Silke Kietz ; Thomas M. Stulnig ; Paolo Parini and Jan-Å ; ke Gustafsson
• 关键词：Liver X Receptor ; Serum glucose levels ; Insulin receptor substrate 2
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2006
• 出版时间：15 September 2006
• 年：2006
• 卷：348
• 期：1
• 页码：176-182
• 全文大小：134 K

文摘

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.