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Related Experiment Videos

Leptin rapidly activates PPARs in C2C12 muscle cells.

Paola Bendinelli1, Roberta Piccoletti, Paola Maroni

  • 1Istituto di Patologia Generale, Università degli Studi di Milano, Italy.

Biochemical and Biophysical Research Communications
|May 24, 2005
PubMed
Summary

Leptin enhances gene expression in skeletal muscle by activating peroxisome proliferator-activated receptors (PPARs) via the ERK-cPLA2 pathway. This study reveals a direct hormonal effect on muscle transcription.

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Area of Science:

  • Molecular Biology
  • Cellular Physiology
  • Endocrinology

Background:

  • Leptin is a hormone known to regulate energy balance and metabolism.
  • Evidence suggests leptin influences gene expression in various tissues, including skeletal muscle.
  • Peroxisome proliferator-activated receptors (PPARs) are key regulators of gene expression involved in metabolism.

Purpose of the Study:

  • To investigate the molecular mechanisms by which leptin modulates gene expression in skeletal muscle cells.
  • To determine if leptin's effect on skeletal muscle involves PPARs.
  • To elucidate the signaling pathway mediating leptin's action on PPARs.

Main Methods:

  • Electrophoretic mobility shift assays (EMSA) to assess DNA-binding activity of PPARs.
  • Treatment of C2C12 myoblasts with leptin and specific inhibitors (AACOCF3, PD-98059).

Related Experiment Videos

  • Measurement of cytosolic phospholipase A2 (cPLA2) activity and phosphorylation.
  • Evaluation of ERK pathway activation.
  • Main Results:

    • Leptin treatment increased the binding of C2C12 nuclear extracts to PPAR response elements.
    • All three PPAR isoforms were found to participate in leptin-induced DNA-binding complexes.
    • Inhibition of cPLA2 (cytosolic phospholipase A2) abrogated leptin-induced PPAR DNA-binding activity.
    • Leptin significantly increased cPLA2 activity and phosphorylation, mediated through ERK induction.

    Conclusions:

    • Leptin directly affects skeletal muscle cells.
    • Leptin modulates muscle transcription through the early activation of PPARs.
    • The ERK-cPLA2 signaling pathway is crucial for leptin-induced PPAR activation in skeletal muscle.