4.7 Article

Xanthigen Suppresses Preadipocyte Differentiation and Adipogenesis through Down-regulation of PPARγ and C/EBPs and Modulation of SIRT-1, AMPK, and FoxO Pathways

期刊

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 60, 期 4, 页码 1094-1101

出版社

AMER CHEMICAL SOC
DOI: 10.1021/jf204862d

关键词

Xanthigen; 3T3-L1 adipocyte; differentiation; SIRT1; PPAR gamma; AMPK; FoxO; C/EBPs

资金

  1. National Science Council, NSC [98-2313-B-022-002-MY3, 100-2321-B-022-001]

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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)gamma, CCAAT/enhancer binding protein (C/EBP) beta, and C/EBP delta 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.

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