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Retinoblastoma Protein Knockdown Favors Oxidative Metabolism and Glucose and Fatty Acid Disposal in Muscle Cells.
Journal article

Retinoblastoma Protein Knockdown Favors Oxidative Metabolism and Glucose and Fatty Acid Disposal in Muscle Cells.

  • Petrov PD Laboratory of Molecular Biology, Nutrition and Biotechnology-Nutrigenomics, Universitat de les Illes Balears, Palma de Mallorca, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Spain.
  • Ribot J Laboratory of Molecular Biology, Nutrition and Biotechnology-Nutrigenomics, Universitat de les Illes Balears, Palma de Mallorca, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Spain.
  • López-Mejía IC Department of Physiology, Université de Lausanne, Switzerland.
  • Fajas L Department of Physiology, Université de Lausanne, Switzerland.
  • Palou A Laboratory of Molecular Biology, Nutrition and Biotechnology-Nutrigenomics, Universitat de les Illes Balears, Palma de Mallorca, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Spain.
  • Bonet ML Laboratory of Molecular Biology, Nutrition and Biotechnology-Nutrigenomics, Universitat de les Illes Balears, Palma de Mallorca, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Spain.
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  • 2015-08-05
Published in:
  • Journal of cellular physiology. - 2016
Animals
Fatty Acids
Gene Knockdown Techniques
Glucose
Insulin
Mice
Muscle Development
Muscle Fibers, Skeletal
Muscle, Skeletal
Oxidation-Reduction
Retinoblastoma Protein
English Deficiency in the retinoblastoma protein (Rb) favors leanness and a healthy metabolic profile in mice largely attributed to activation of oxidative metabolism in white and brown adipose tissues. Less is known about Rb modulation of skeletal muscle metabolism. This was studied here by transiently knocking down Rb expression in differentiated C2C12 myotubes using small interfering RNAs. Compared with control cells transfected with non-targeting RNAs, myotubes silenced for Rb (by 80-90%) had increased expression of genes related to fatty acid uptake and oxidation such as Cd36 and Cpt1b (by 61% and 42%, respectively), increased Mitofusin 2 protein content (∼2.5-fold increase), increased mitochondrial to nuclear DNA ratio (by 48%), increased oxygen consumption (by 65%) and decreased intracellular lipid accumulation. Rb silenced myotubes also displayed up-regulated levels of glucose transporter type 4 expression (∼5-fold increase), increased basal glucose uptake, and enhanced insulin-induced Akt phosphorylation. Interestingly, exercise in mice led to increased Rb phosphorylation (inactivation) in skeletal muscle as evidenced by immunohistochemistry analysis. In conclusion, the silencing of Rb enhances mitochondrial oxidative metabolism and fatty acid and glucose disposal in skeletal myotubes, and changes in Rb status may contribute to muscle physiological adaptation to exercise.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/46388
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