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Mitogen-activated protein kinase activation is not necessary for, but antagonizes, 3T3-L1 adipocytic differentiation

J Font de Mora1, A Porras, N Ahn

  • 1Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Molecular and Cellular Biology
|October 7, 1997
PubMed

Insights

Mitogen-activated protein kinase (MAPK) activation by insulin does not drive adipocyte differentiation and may inhibit it. Blocking MAPK with PD98059 enhanced differentiation and reversed inhibition by TNF-alpha.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Ras proteins are key mediators of insulin signaling in 3T3-L1 fibroblasts, influencing adipocyte differentiation and kinase activation.
  • Mitogen-activated protein kinase (MAPK) is activated by insulin and Ras, but its role in adipogenesis is unclear.

Purpose of the Study:

  • To investigate the role of MAPK activation in insulin-induced adipocyte differentiation.
  • To determine if MAPK activation is necessary for or antagonistic to adipogenesis.

Main Methods:

  • Utilized MEK-specific inhibitor PD98059 to block MAPK activation in 3T3-L1 preadipocytes.
  • Examined the effects of PD98059 on insulin- and Ras-induced differentiation.
  • Investigated the impact of TNF-alpha on MAPK activation and adipogenesis, and the effect of PD98059.
  • Analyzed differentiation in 3T3-L1 cells with hyperactivated MEK1 or overexpressed MAPK.

Main Results:

  • PD98059 inhibited insulin- and Ras-induced MAPK activation without impairing adipocytic differentiation, and sometimes enhanced it.
  • Tumor necrosis factor alpha (TNF-alpha) activated MAPK and inhibited adipogenesis; PD98059 blocked TNF-alpha-induced MAPK activation and reversed low-dose TNF-alpha-mediated inhibition.
  • Hyperactivation or overexpression of MEK1 or MAPK impaired adipocytic differentiation, an effect reversed by PD98059.

Conclusions:

  • MAPK activation is not required for insulin-induced adipocyte differentiation and actively antagonizes the process.
  • Inhibiting MAPK signaling can enhance adipogenesis and overcome inhibitory signals like TNF-alpha.
  • MAPK pathway plays an inhibitory role in 3T3-L1 adipocytic differentiation.

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