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Publication : LXR{beta} is the dominant LXR subtype in skeletal muscle regulating lipogenesis and cholesterol efflux.

First Author  Hessvik NP Year  2010
Journal  Am J Physiol Endocrinol Metab Volume  298
Issue  3 Pages  E602-13
PubMed ID  19996385 Mgi Jnum  J:169945
Mgi Id  MGI:4943621 Doi  10.1152/ajpendo.00553.2009
Citation  Hessvik NP, et al. (2010) LXR{beta} is the dominant LXR subtype in skeletal muscle regulating lipogenesis and cholesterol efflux. Am J Physiol Endocrinol Metab 298(3):E602-13
abstractText  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.
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