Xanthigen suppresses preadipocyte differentiation and adipogenesis through down-regulation of PPARγ and C/EBPs and modulation of SIRT-1, AMPK, and FoxO pathways

J Agric Food Chem. 2012 Feb 1;60(4):1094-101. doi: 10.1021/jf204862d. Epub 2012 Jan 17.


Xanthigen is a source of punicic acid and fucoxanthin derived from pomegranate seed and brown seaweed, respectively with recognized triacylglycerol-lowering effects in humans, yet the mechanism remains to be fully elucidated. The present study investigated the inhibitory effects of Xanthigen, fucoxanthin, and punicic acid (70% in pomegranate seed oil) on the differentiation of 3T3-L1 preadipocytes. Xanthigen potently and dose-dependently suppressed accumulation of lipid droplets in adipocytes compared to its individual components, fucoxanthin and pomegranate seed oil. Western blot analysis revealed that Xanthigen markedly down-regulated the protein levels of key adipogenesis transcription factors peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer binding protein (C/EBP) β, and C/EBPδ as well as a key enzyme involved in adipogenesis, fatty acid synthase (FAS). Xanthigen up-regulated the NAD(+)-dependent histone deacetylases (SIRT1) and activated AMP-activated protein kinase (AMPK) signaling in differentiated 3T3-L1 adipocytes. In addition, Xanthigen may also stimulate insulin trigger signaling and result in Akt-dependent phosphorylation of forkhead/winged helix O (FoxO)1 and FoxO3a. These results indicate that Xanthigen suppresses adipocyte differentiation and lipid accumulation through multiple mechanisms and may have applications for the treatment of obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / metabolism
  • Adipocytes / cytology*
  • Adipocytes / drug effects
  • Adipogenesis / drug effects*
  • Animals
  • CCAAT-Enhancer-Binding Proteins / analysis*
  • Cell Differentiation / drug effects*
  • Down-Regulation
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Infant
  • Linolenic Acids / pharmacology
  • Mice
  • PPAR gamma / analysis*
  • Plant Extracts / pharmacology*
  • Signal Transduction
  • Sirtuin 1 / metabolism
  • Xanthophylls / pharmacology


  • CCAAT-Enhancer-Binding Proteins
  • Forkhead Transcription Factors
  • Linolenic Acids
  • PPAR gamma
  • Plant Extracts
  • Xanthophylls
  • xanthigen
  • fucoxanthin
  • AMP-Activated Protein Kinases
  • Sirt1 protein, mouse
  • Sirtuin 1
  • punicic acid