LXRß is the dominant LXR subtype in skeletal muscle regulating lipogenesis and cholesterol efflux

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 LXR and LXRß 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 LXR and LXRß knockout (KO) mice were established. The present study showed that treatment with the LXR agonist T0901317 increased lipogenesis and apoA1-dependent cholesterol efflux in LXR KO and WT myotubes but not in LXRß 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 LXR KO mice, whereas only minor changes were observed for these genes in myotubes from LXRß 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 LXRß KO myotubes compared with WT myotubes, suggesting a role for LXRß in glucose metabolism in skeletal muscle. In conclusion, LXRß seems to be the main LXR subtype regulating lipogenesis and cholesterol efflux in skeletal muscle