Modest Decrease in Pgc1α Results in TAG Accumulation but not in Insulin Resistance in L6 Myotubes

• Main Authors: Bartlomiej Lukaszuk, Agnieszka Miklosz, Adrian Chabowski, Jan Górski
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2015-03-01
• Series: Cellular Physiology and Biochemistry
• Subjects: PGC-1α Lipids; Mitochondria; Skeletal muscle; Insulin resistance
• Online Access: http://www.karger.com/Article/FullText/373975

Background/Aims: 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.