p300 Is Not Required for Metabolic Adaptation to Endurance Exercise Training

FASEB J. 2016 Apr;30(4):1623-33. doi: 10.1096/fj.15-281741. Epub 2015 Dec 28.

Abstract

The acetyltransferase, E1a-binding protein (p300), is proposed to regulate various aspects of skeletal muscle development, metabolism, and mitochondrial function,viaits interaction with numerous transcriptional regulators and other proteins. Remarkably, however, the contribution of p300 to skeletal muscle function and metabolism,in vivo, is poorly understood. To address this, we used Cre-LoxP methodology to generate mice with skeletal muscle-specific knockout of E1a-binding protein (mKO). mKO mice were indistinguishable from their wild-type/floxed littermates, with no differences in lean mass, skeletal muscle structure, fiber type, respirometry flux, or metabolites of fatty acid and amino acid metabolism.Ex vivomuscle function in extensor digitorum longus and soleus muscles, including peak stress and time to fatigue, as well asin vivorunning capacity were also comparable. Moreover, expected adaptations to a 20 d voluntary wheel running regime were not compromised in mKO mice. Taken together, these findings demonstrate that p300 is not required for the normal development or functioning of adult skeletal muscle, nor is it required for endurance exercise-mediated mitochondrial adaptations.-LaBarge, S. A., Migdal, C. W., Buckner, E. H., Okuno, H., Gertsman, I., Stocks, B., Barshop, B. A., Nalbandian, S. R., Philp, A., McCurdy, C. E., Schenk, S. p300 is not required for metabolic adaptation to endurance exercise training.

Keywords: acetyltransferase; knockout; metabolomics; mitochondria; physiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / genetics
  • Adaptation, Physiological / physiology*
  • Amino Acids / metabolism
  • Animals
  • E1A-Associated p300 Protein / genetics
  • E1A-Associated p300 Protein / metabolism*
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology
  • Fatty Acids / metabolism
  • Gene Expression
  • Immunoblotting
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / genetics
  • Motor Activity / physiology
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / metabolism*
  • Physical Conditioning, Animal / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Amino Acids
  • Fatty Acids
  • Muscle Proteins
  • E1A-Associated p300 Protein