PGC1alpha expression is controlled in skeletal muscles by PPARbeta, whose ablation results in fiber-type switching,

Michael Schuler1, Faisal Ali, Céline Chambon

  • 1IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Department of Physiological Genetics, Illkirch, F-67400 France.

Cell Metabolism
|November 7, 2006
PubMed

Insights

Peroxisome proliferator-activated receptor beta (PPARbeta) is crucial for maintaining oxidative muscle fibers. Its ablation in myocytes causes fiber-type switching, leading to obesity and diabetes, not the other way around.

Area of Science:

  • Muscle physiology
  • Metabolic disorders
  • Molecular biology

Background:

  • Peroxisome proliferator-activated receptor beta (PPARbeta) is a nuclear receptor involved in various cellular processes.
  • Skeletal muscle's oxidative capacity is critical for metabolic health.
  • Dysregulation of muscle metabolism is linked to obesity and diabetes.

Purpose of the Study:

  • To investigate the role of PPARbeta signaling specifically within skeletal muscle myocytes.
  • To determine if PPARbeta influences muscle fiber type and oxidative capacity.
  • To elucidate the connection between PPARbeta, muscle fiber type, and metabolic disorders.

Main Methods:

  • Generation of mice with selective ablation of PPARbeta in skeletal muscle myocytes.
  • Analysis of muscle fiber type composition and oxidative capacity.
  • Investigation of gene expression, including PGC1alpha, in response to PPARbeta signaling.

Main Results:

  • Selective PPARbeta ablation in myocytes induced a shift towards less oxidative muscle fibers.
  • This fiber-type switching preceded the onset of obesity and diabetes in the mutant mice.
  • PPARbeta was shown to stimulate the expression of PGC1alpha, a key factor in slow muscle fiber formation.

Conclusions:

  • PPARbeta signaling in myocytes is essential for maintaining oxidative muscle fibers.
  • Muscle fiber-type switching, driven by PPARbeta deficiency, is a likely cause of metabolic disorders like obesity and diabetes.
  • PPARbeta's role in promoting slow muscle fiber formation is, in part, mediated by transcriptional stimulation of PGC1alpha.

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