title: Leptin rapidly induces the expression of metabolic and myokine genes in C2C12 muscle cells to regulate nutrient partition and oxidation.
abstract: 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 50 ng/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 γ coactivator 1α (PGC1α) protein levels by western blot.
  
  
  RESULTS
  The most significant effects were observed with 50 ng/ml leptin. In the short-term (30' and/or 3h), leptin significantly induced the expression of PGC1α, 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). PGC1α protein levels were increased (24h).
  
  
  CONCLUSIONS
  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 PGC1α, mCPT1, UCP3, PDK4 and the signaling secretory molecule IL6 particularly interesting.
authors.affiliation: Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics), University of the Balearic Islands (UIB) and CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Spain.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Nozhenko
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rodríguez
authors.forename: Andreu
authors.initials: A
authors.lastname: Palou
mesh_terms: D000818:Animals; D002460:Cell Line; D053818:Chymases / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071247:Uncoupling Protein 3; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D019409:Interleukin-15; D015850:Interleukin-6; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; C000631439:Pdk4 protein, mouse; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger; D014157:Transcription Factors; C000604393:Ucp3 protein, mouse; D000071247:Uncoupling Protein 3; D011972:Receptor, Insulin; D017346:Protein Serine-Threonine Kinases; D053818:Chymases; C509230:Mcpt1 protein, mouse