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Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice

Bárbara de Almeida Rodrigues1, Gabriel Keine Kuga2, Vitor Rosetto Muñoz1

  • 1School of Applied Sciences, University of Campinas, Limeira, SP, Brazil.

Neuroscience Letters
|September 4, 2017
PubMed

Insights

Mitogen-activated kinase phosphatase-3 (MKP-3) regulates cell cycle by dephosphorylating FoxO1. Hypothalamic MKP-3 overexpression reduces insulin signaling

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Endocrinology

Background:

  • Mitogen-activated kinase phosphatase-3 (MKP-3) dephosphorylates FoxO1, a transcription factor crucial for insulin signaling.
  • Insulin signaling normally inhibits orexigenic neuropeptides (NPY/AgRP) by preventing FoxO1 nuclear translocation.
  • The role of MKP-3 in hypothalamic insulin signaling and FoxO1 phosphorylation remains unclear.

Purpose of the Study:

  • To investigate the effect of MKP-3 overexpression on FoxO1 phosphorylation in the hypothalamus.
  • To determine if MKP-3 influences the insulin signaling pathway's capacity to phosphorylate FoxO1.

Main Methods:

  • Overexpression of the DUSP6 gene (encoding MKP-3) in the hypothalamus of Swiss mice using adenovirus injection.
  • Confirmation of adenovirus colocalization via immunofluorescence assay.
  • Assessment of hypothalamic FoxO1 and Akt phosphorylation levels following insulin stimulation.

Main Results:

  • MKP-3 overexpression significantly reduced FoxO1 phosphorylation in response to insulin stimulation.
  • This reduction in FoxO1 phosphorylation was independent of changes in Akt phosphorylation.
  • Immunofluorescence confirmed successful adenovirus-mediated gene delivery to the hypothalamus.

Conclusions:

  • Hypothalamic MKP-3 plays a role in dephosphorylating FoxO1, modulating insulin signaling.
  • MKP-3 may serve as a therapeutic target for hypothalamic disorders linked to obesity and appetite control.
  • Further research into MKP-3's function could elucidate mechanisms of energy balance regulation.
Keywords:
HypothalamusInsulinMKP-3

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