Xanthigen suppresses preadipocyte differentiation and adipogenesis through down-regulation of PPARγ and C/EBPs and modulation of SIRT-1, AMPK, and FoxO pathways.
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.
Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung, Taiwan.
Ching-Shu
CS
Lai
Mei-Ling
ML
Tsai
Vladimir
V
Badmaev
Miguel
M
Jimenez
Chi-Tang
CT
Ho
Min-Hsiung
MH
Pan
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000032:analysis*; D002454:Cell Differentiation / Q000187:drug effects*; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007223:Infant; D008042:Linolenic Acids / Q000494:pharmacology; D051379:Mice; D047495:PPAR gamma / Q000032:analysis*; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism; D024341:Xanthophylls / Q000494:pharmacology
D022762:CCAAT-Enhancer-Binding Proteins; D051858:Forkhead Transcription Factors; D008042:Linolenic Acids; D047495:PPAR gamma; D010936:Plant Extracts; D024341:Xanthophylls; C571403:xanthigen; C025164:fucoxanthin; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; C519714:punicic acid