LXR{beta} is the dominant LXR subtype in skeletal muscle regulating lipogenesis and cholesterol efflux
Autor: | Sander Kersten, Xiufeng Xu, G. H. Thoresen, Arild Chr. Rustan, Nina Pettersen Hessvik, M. A. Baltzersen, Harriet Andersén, Mark V. Boekschoten |
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Rok vydání: | 2009 |
Předmět: |
Physiology
Endocrinology Diabetes and Metabolism oxysterol receptor Adipose tissue induced insulin-resistance adipose-tissue glucose-metabolism Myoblasts chemistry.chemical_compound Voeding Metabolisme en Genomica Mice polycyclic compounds nuclear receptor Cells Cultured Liver X Receptors Feedback Physiological Mice Knockout deficient mice Orphan Nuclear Receptors Metabolism and Genomics medicine.anatomical_structure Cholesterol Metabolisme en Genomica Lipogenesis lipids (amino acids peptides and proteins) Nutrition Metabolism and Genomics medicine.medical_specialty fatty-acid oxidation Carbohydrate metabolism Biology digestive system Voeding Physiology (medical) Internal medicine medicine Animals Liver X receptor Muscle Skeletal Nutrition VLAG liver-x-receptors Skeletal muscle Lipid metabolism Lipid Metabolism signaling pathways Endocrinology Nuclear receptor chemistry lipid-metabolism |
Zdroj: | American Journal of Physiology. Endocrinology and Metabolism, 298, E602-E613 American Journal of Physiology. Endocrinology and Metabolism 298 (2010) |
ISSN: | 1522-1555 0193-1849 |
Popis: | Liver X receptors (LXRs) are important regulators of cholesterol, lipid, and glucose metabolism and have been extensively studied in liver, macrophages, and adipose tissue. However, their role in skeletal muscle is poorly studied and the functional role of each of the LXRalpha and LXRbeta subtypes in skeletal muscle is at present unknown. To study the importance of each of the receptor subtypes, myotube cultures derived from wild-type (WT) and LXRalpha and LXRbeta knockout (KO) mice were established. The present study showed that treatment with the LXR agonist T0901317 increased lipogenesis and apoA1-dependent cholesterol efflux in LXRalpha KO and WT myotubes but not in LXRbeta KO cells. The functional studies were confirmed by T0901317-induced increase in mRNA levels of LXR target genes involved in lipid and cholesterol metabolism in myotubes established from WT and LXRalpha KO mice, whereas only minor changes were observed for these genes in myotubes from LXRbeta KO mice. Gene expression analysis using microarrays showed that very few genes other than the classical, well-known LXR target genes were regulated by LXR in skeletal muscle. The present study also showed that basal glucose uptake was increased in LXRbeta KO myotubes compared with WT myotubes, suggesting a role for LXRbeta in glucose metabolism in skeletal muscle. In conclusion, LXRbeta seems to be the main LXR subtype regulating lipogenesis and cholesterol efflux in skeletal muscle. |
Databáze: | OpenAIRE |
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