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Capmatinib attenuates lipogenesis in 3T3-L1 adipocytes through an adenosine monophosphate-activated protein

Sung Ho Ahn1, Hyun Jung Lee2, Do Hyeon Pyun3

  • 1Department of Pathology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.

Biochemical and Biophysical Research Communications
|March 23, 2021
PubMed

Insights

Capmatinib (CAP) effectively reduces fat accumulation and promotes fat breakdown in adipocytes. This novel obesity therapeutic targets the irisin/AMPK pathway for its anti-obesity effects.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Metabolic Research

Background:

  • Obesity incidence is rapidly increasing globally.
  • Effective therapeutic agents for obesity remain limited.
  • Capmatinib (CAP), a MET inhibitor, shows potential anti-inflammatory and anti-oxidative properties.

Purpose of the Study:

  • To investigate the effects of Capmatinib (CAP) on lipogenesis in adipocytes.
  • To elucidate the molecular mechanisms underlying CAP's potential anti-obesity effects.

Main Methods:

  • 3T3-L1 adipocytes were treated with varying doses of CAP.
  • Lipid accumulation, differentiation, and lipolysis were assessed.
  • Adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and FNDC5 expression were measured.
  • Gene silencing (si-AMPK, si-FNDC5) was employed to investigate pathway involvement.

Main Results:

  • CAP dose-dependently suppressed lipid accumulation and adipocyte differentiation.
  • CAP treatment increased lipolysis in 3T3-L1 adipocytes.
  • CAP augmented AMPK phosphorylation and FNDC5 expression.
  • Silencing AMPK or FNDC5 reversed CAP's effects on lipogenesis and lipolysis.
  • FNDC5 silencing also reduced CAP-induced AMPK phosphorylation.

Conclusions:

  • Capmatinib (CAP) demonstrates anti-obesity effects by suppressing lipogenesis and enhancing lipolysis in adipocytes.
  • The anti-obesity mechanism of CAP involves the irisin/AMPK pathway.
  • CAP represents a potential novel therapeutic agent for obesity treatment.
Keywords:
AMPKAdipocyteCapmatinibIrisinLipogenesisLipolysis

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