title: Modest decrease in PGC1α results in TAG accumulation but not in insulin resistance in L6 myotubes.
abstract: OBJECTIVE
  PGC-1α is an important cellular protein (coactivator) regulating myocyte mitochondria number and function, and therefore whole cellular energy status. The aim of this work was to investigate the effects of modest, temporary PGC-1α knock-down on L6 myotubes insulin resistance in a light of cellular lipid metabolism.
  
  
  METHODS
  Gas liquid chromatography was applied for assessing FAs content and composition. For the expression of mitochondrial enzymes, as well as FA and glucose transporters, Western Blot technique was adopted. Additionally, radiolabelled glucose and palmitic acid uptake was performed to estimate the nutrients cellular influx.
  
  
  RESULTS
  Modest (-24%) PGC-1α protein ablation resulted in decreased mitochondrial activity in general (reduced Cyt C content) and FAs oxidation in particular (diminished β-HAD expression) without increased FAs cellular influx. The aforementioned intervention led to significantly increased TAG cellular level, but not DAG nor CER. Consequently, no changes in cellular insulin responsiveness were noticed.
  
  
  CONCLUSIONS
  Modest (-24%) PGC-1α protein depletion results in lipid accumulation, without causing insulin resistance. Importantly, it seems that this TAG loading is a result of decreased mitochondrial oxidative capacity and/or possibly increased lipid biosynthesis but not fatty acid cellular influx.
authors.affiliation: Department of Physiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Lukaszuk
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Miklosz
authors.forename: Adrian
authors.initials: A
authors.lastname: Chabowski
authors.forename: Jan
authors.initials: J
authors.lastname: Górski
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002518:Ceramides / Q000378:metabolism; D002849:Chromatography, Gas; D004075:Diglycerides / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D002518:Ceramides; D004075:Diglycerides; D005227:Fatty Acids; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014280:Triglycerides; D019308:Palmitic Acid; D005947:Glucose