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
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