Sulforaphene Inhibition of Adipogenesis via Hedgehog Signaling in 3T3-L1 Adipocytes

J Agric Food Chem. 2018 Nov 14;66(45):11926-11934. doi: 10.1021/acs.jafc.8b04330. Epub 2018 Nov 1.

Abstract

Obesity is a risk factor for numerous metabolic disorders. In this study, we investigated the effects of the isothiocyanates sulforaphane (SA) and sulforaphene (SE) on adipogenesis in 3T3-L1 adipocytes. SE, a compound that is abundant in radish, inhibited adipogenesis by suppressing the adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ, 69.2 ± 2.4%, P < 0.05) and CCAAT/enhancer-binding protein α (C/EBPα, 36.1 ± 3.1%, P < 0.05), thereby reducing fat accumulation in 3T3-L1 adipocytes (45.6 ± 2.7%, P < 0.05); SA was less effective. SE exerted these activities through the activation of the Hedgehog (Hh) signaling pathway by restoring Smo ((2.1 ± 0.2)-fold, P < 0.05) and Gli1 ((2.8 ± 0.1)-fold, P < 0.05) expression, which was suppressed by adipogenic signals. These effects of SE were abrogated by treatment with the Hh inhibitor vismodegib. Thus, SE inhibits adipocyte differentiation via Hh signaling and may be an effective natural agent for preventing adipocyte hyperplasia and obesity.

Keywords: 3T3-L1 adipocytes; adipogenesis; adipogenic transcription factors; hedgehog signaling; sulforaphene.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Anti-Obesity Agents / pharmacology*
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Hedgehogs / genetics
  • Hedgehogs / metabolism*
  • Isothiocyanates / pharmacology*
  • Mice
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Signal Transduction / drug effects

Substances

  • Anti-Obesity Agents
  • CCAAT-Enhancer-Binding Protein-alpha
  • Isothiocyanates
  • PPAR gamma
  • sulphoraphene