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oai:repisalud.isciii.es:20.500.12105/201682024-11-28T21:50:06Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Nozhenko, Yuriy author Rodriguez, Ana M. author Palou, Andreu author 2015 Background: Skeletal muscle can experience pronounced metabolic adaptations in response to extrinsic stimuli, and expresses leptin receptor (OB-Rb). We aimed to further the understanding of leptin effects on muscle cells, by studying the expression of key energy metabolism genes in C2C12 myotubes. Methods: We performed a dose-time-dependent study with physiological concentrations of leptin: 5, 10 and 50ng/ml, for 0, 30', 3h, 6h, 12h and 24h, also monitoring time-course changes in non-treated cells. mRNA levels were analyzed by RT-qPCR and peroxisome proliferator activated receptor. coactivator 1 alpha (PGC1 alpha) protein levels by western blot. Results: The most significant effects were observed with 50ng/ml leptin. In the short-term (30' and/or 3h), leptin significantly induced the expression of PGC1 alpha, muscle carnitine palmitoyl transferase 1 (mCPT1), uncoupling protein 3 (UCP3), OB-Rb, Insulin receptor (InsR) and interleukins 6 and 15 (IL6, IL15). There was a decrease in mRNA levels of pyruvate dehydrogenase kinase 4 (PDK4) and mCPT1 in the long-term (24h). PGC1 alpha protein levels were increased (24h). Conclusion: Leptin rapidly induces the expression of genes important for its own response and the control of metabolic fuels, with the rapid responses of the genes encoding the master regulator PGC1 alpha, mCPT1, UCP3, PDK4 and the signaling secretory molecule IL6 particularly interesting. Nozhenko Y, Rodriguez Guerrero AM, Palou Oliver A. Leptin Rapidly Induces the Expression of Metabolic and Myokine Genes in C2C12 Muscle Cells to Regulate Nutrient Partition and Oxidation. Cell Physiol Biochem. 2015;35(1):92-103. Epub 2015 Jan 2. 10.1159/000369678 1421-9778 1015-8987 Cellular Physiology and Biochemistry http://hdl.handle.net/20.500.13003/11680 25547246 L601298357 2-s2.0-84920804301 http://hdl.handle.net/20.500.12105/20168 348048000009 Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) Uncoupling proteins (UCPs) Muscle carnitine palmitoyl transferase 1 (mCPT1) Pyruvate dehydrogenase kinase 4 (PDK4) Interleukins Leptin Rapidly Induces the Expression of Metabolic and Myokine Genes in C2C12 Muscle Cells to Regulate Nutrient Partition and Oxidation