Pharmacological activation of PPARβ promotes rapid and calcineur-independent fiber remodeling and angiogenesis in mouse skeletal muscle

Céline Gaudel, Chantal Schwartz, Christian Giordano, Nada A. Abumrad, Paul A. Grimaldi

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Recent studies have shown that administration of peroxisome proliferator-activated receptor-β (PPARβ) agonists enhances fatty acid oxidation in rodent and human skeletal muscle and that musclerestricted PPARβ overexpression affects muscle metabolic profile by increasing oxidative myofiber number, which raises the possibility that PPARβ agonists alter muscle morphology in adult animals. This possibility was examined in this study in which adult mice were treated with a PPARβ agonist, and the resulting changes in myofiber metabolic phenotype and angiogenesis were quantified in tibialis anterior muscles. The findings indicate a muscle remodeling that is completed within 2 days and is characterized by a 1.63-fold increase in oxidative fiber number and by a 1.55-fold increase in capillary number. These changes were associated with a quick and transient upregulation of myogenic and angiogenic markers. Both myogenic and angiogenic responses were dependent on the calcineurin pathway, as they were blunted by cyclosporine A administration. In conclusion, the data indicate that PPARβ activation is associated with a calcineurin-dependent effect on muscle morphology that enhances the oxidative phenotype.

Original languageEnglish
Pages (from-to)E297-E304
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume295
Issue number2
DOIs
StatePublished - Aug 1 2008

Keywords

  • Metabolism
  • Myogenesis
  • Type 2 diabetes

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