Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells |
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Authors: | A Bolado-Carrancio JA Riancho J Sainz JC Rodríguez-Rey |
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Institution: | 1. Department of Molecular Biology, University of Cantabria, IDIVAL, Santander, Spain;2. Department of Internal Medicine, Hospital U.M. Valdecilla-IDIVAL, University of Cantabria, RETICEF, Santander, Spain;3. Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC-University of Cantabria, Santander, Spain |
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Abstract: | NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Because skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose levels and restores insulin sensitivity. |
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Keywords: | NR5A2 nuclear receptor subfamily 5 group A member GLUT4 glucose transporter 4 Acc2 acetyl-CoA carboxylase 2 DLPC dilauroyl phosphatidylcholine CEPT Cholesteryl ester transfer protein CYP7A1 cholesterol 7 alpha-hydroxylase CYP8B1 sterol 12-alpha-hydroxylase T2DM type 2 diabetes mellitus DMEM Dulbecco&rsquo s modified Eagle&rsquo s medium Myog myogenin MyoD myogenic differentiation 1 Hk2 hexokinase 2 Pkfm muscle phosphofructokinase PfkFb1 6-phosphofructo-2-kinase/fructose-2 6-biphosphatase 1 Gys1 muscle glycogen synthase Pygm muscle glycogen phosphorylase Mef2c myocyte-specific enhancer factor 2C Pgc1α peroxisome proliferator activated receptor gamma coactivator 1 alpha Pparα peroxisome proliferator activated receptor alpha Cpt1b muscular carnitine palmitoyltransferase 1 Vldlr very low density lipoprotein receptor Lpl lipoprotein lipase Fabp3 muscular fatty acid binding protein S D standard deviation |
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