Putative Metabolic Effects of the Liver X Receptor (LXR)
- Address correspondence and reprint requests to Jan-Åke Gustafsson, Department of Medical Nutrition and Biosciences, Karolinska Institutet, S-14157 Huddinge, Sweden. E-mail: jan-ake.gustafsson{at}mednut.ki.se
Abstract
The nuclear receptors liver X receptor (LXR)α and LXRβ are sensors of cholesterol metabolism and lipid biosynthesis. They have recently been found to be regulators of inflammatory cytokines, suppressors of hepatic glucose production, and involved in different cell-signaling pathways. LXRα is a target gene of the peroxisome proliferator-activated receptor-γ, a target of drugs used in treating elevated levels of glucose seen in diabetes. Furthermore, insulin induces LXRα in hepatocytes, resulting in increased expression of lipogenic enzymes and suppression of key enzymes in gluconeogenesis, including PEPCK. LXR seems to have an important role in the regulation of glucocorticoid action and a role in the overall energy homeostasis suggested by its putative regulatory effect on leptin and uncoupling protein 1. The physiological roles of LXR indicate that it is an interesting potential target for drug treatment of diabetes.
- 11β-HSD1, 11β-hydroxysteroid dehydrogenase type 1
- Angptl3, angiopoietin-like protein 3
- IL, interleukin
- LXR, liver X receptor
- PPAR, peroxisome proliferator-activated receptor
- SCD, stearoyl CoA desaturase
- SREBP, sterol response element-binding protein
- TNF, tumor necrosis factor
- WAT, white adipose tissue
Footnotes
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This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Les Laboratoires Servier.
J.-Å.G. serves on an advisory panel for, holds stock in, and has received honoraria and grant support from KaroBio AB.
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- Accepted May 20, 2003.
- Received March 14, 2003.
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