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

Abstract

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.

Fucoxanthin and lipid metabolism: A minireview

“…The high efficiency of xanthigen in improving the lipid metabolism was shown in both experimental and clinical studies. In the in vitro study on 3T3-L1 preadipocytes, xanthigen suppressed the adipocyte differentiation and accumulation of lipid droplets more efficiently than its components, FX and pomegranate seed oil [43]. Further analysis revealed that among key events which could mediate these effects are downregulation of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding proteins (C/EBP) β and δ, and fatty acid synthase, with concomitant upregulation of AMP-activated protein kinase signaling pathways [43].…”

A Review of Natural Stimulant and Non‐stimulant Thermogenic Agents

“…Lai et al (2012) investigated the effects of fucoxanthin combined with pomegranate seed oil standardized for punicic acid in a compound formula (Xanthigen®). The combination of these two supplements suppressed accumulation of lipid droplets in adipocytes, downregulated PPARγ, cytosine‐cytosine‐adenosine‐adenosine‐thymidine (CCAAT)/enhancer binding protein, and fatty acid synthase.…”

Anti-Cancer Mechanism and Possibility of Nano-Suspension Formulation for a Marine Algae Product Fucoxanthin

“…Fucoxanthin is converted to fucoxanthinol and amarouciaxanthin-A. This metabolite of fucoxanthin in white adipose tissue suppresses adipocyte differentiation and development (Yim et al, 2011;Lai et al, 2012) investigated the inhibitory effects of fucoxanthin, on the differentiation of preadipocytes and recognized as triacylglycerol-lowering agent in humans which is also observed by (Hu et al, 2012).…”