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Phenethyl Isothiocyanate (PEITC) interaction with Keap1 activates the Nrf2 pathway and inhibits lipid accumulation in

Hae-Sun Ko1, Kwonyoung Kim2, Yu-Ran Na3

  • 1Department of Food Science and Biotechnology, Food Clinical Research Center, Sungkyunkwan University, Suwon, Republic of Korea.

The Journal of Nutritional Biochemistry
|May 18, 2025
PubMed

Insights

Phenethyl isothiocyanate (PEITC) inhibits adipocyte differentiation by activating Nrf2. This occurs through direct interaction with Keap1, specifically at cysteine 151, highlighting a novel therapeutic target.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Phenethyl isothiocyanate (PEITC) shows potential in disease treatment.
  • The role of PEITC in adipocyte differentiation and its molecular pathways remain unclear.

Purpose of the Study:

  • To investigate PEITC's effects on adipocyte differentiation.
  • To elucidate the molecular mechanisms of Nrf2 activation by PEITC.

Main Methods:

  • Assessed PEITC effects on adipocyte differentiation in C3H10T1/2 and 3T3-L1 cells.
  • Examined Nrf2 activation in Nrf2 knockout and Keap1 knockout cells.
  • Utilized thermal shift assays, co-immunoprecipitation, and Keap1 cysteine mutant reconstitution.

Main Results:

  • PEITC demonstrated anti-adipogenic effects during early adipogenesis.
  • PEITC increased Nrf2 protein expression, dependent on Keap1.
  • PEITC directly binds Keap1, with Cysteine 151 being crucial for Nrf2 stabilization and anti-adipogenic activity.

Conclusions:

  • PEITC inhibits adipocyte differentiation via Nrf2 activation.
  • PEITC interacts with Keap1 at Cysteine 151, disrupting the Nrf2-Keap1 complex.
  • This study identifies a key mechanism for PEITC's anti-adipogenic effects.
Keywords:
AdipocyteKeap1Keap1-Nrf2 complexesNrf2PEITC

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