Enhanced glucose metabolism is preserved in cultured primary myotubes from obese donors in response to exercise training

J Clin Endocrinol Metab. 2013 Sep;98(9):3739-47. doi: 10.1210/jc.2013-1727. Epub 2013 Jul 24.

Abstract

Context: It was suggested that human cultured primary myotubes retain the metabolic characteristics of their donor in vitro.

Objectives: The aim of the present study was to investigate whether the metabolic responses to endurance training are also conserved in culture.

Design and volunteers: Middle-aged obese subjects completed an 8-week supervised aerobic exercise training program in which vastus lateralis muscle biopsies were collected before and after training.

Main outcome measures: Anthropometric and blood parameters, as well as aerobic capacity, were assessed before and after training. Muscle biopsies were either used for Western blot analysis or digested to harvest myogenic progenitors that were differentiated into myotubes. Glucose oxidation, palmitate oxidation, and glycogen synthesis assays were performed on myotubes before and after training. Gene expression was assessed by real-time quantitative PCR.

Results: Our data indicate that in parallel of in vivo improvement of whole-body aerobic capacity and glucose metabolism, biopsy-derived primary myotubes showed similar patterns in vitro. Indeed, glucose oxidation, glycogen synthesis, and inhibition of palmitate oxidation by glucose were enhanced in myotubes after training. This was associated with consistent changes in the expression of metabolism-linked genes such as GLUT1, PDK4, and PDHA1. Interestingly, no difference in myogenic differentiation capacity was observed before and after training.

Conclusion: Aerobic exercise training is associated with metabolic adaptations in vivo that are preserved in human cultured primary myotubes. It can be hypothesized that skeletal muscle microenvironmental changes induced by endurance training lead to metabolic imprinting on myogenic progenitor cells.

Trial registration: ClinicalTrials.gov NCT01083329.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exercise Therapy*
  • Exercise*
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism
  • Glycogen / biosynthesis
  • Humans
  • Male
  • Middle Aged
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle Fibers, Skeletal / pathology
  • Obesity / metabolism*
  • Obesity / pathology
  • Obesity / therapy
  • Oxidation-Reduction
  • Palmitic Acid / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Pyruvate Dehydrogenase (Lipoamide) / genetics
  • Pyruvate Dehydrogenase (Lipoamide) / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Quadriceps Muscle / metabolism*
  • Quadriceps Muscle / pathology

Substances

  • Glucose Transporter Type 1
  • PDK4 protein, human
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Palmitic Acid
  • Glycogen
  • Pyruvate Dehydrogenase (Lipoamide)
  • pyruvate dehydrogenase E1alpha subunit
  • Protein Serine-Threonine Kinases
  • Glucose

Associated data

  • ClinicalTrials.gov/NCT01083329